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Sample records for hormonal factors modulate

  1. Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

    Science.gov (United States)

    Lecomte, Marie-José; Bertolus, Chloé; Ramanantsoa, Nélina; Saurini, Françoise; Callebert, Jacques; Sénamaud-Beaufort, Catherine; Ringot, Maud; Bourgeois, Thomas; Matrot, Boris; Collet, Corinne; Nardelli, Jeannette; Mallet, Jacques; Vodjdani, Guilan; Gallego, Jorge; Launay, Jean-Marie; Berrard, Sylvie

    2018-04-01

    Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

  2. The corticosteroid hormone induced factor: a new modulator of KCNQ1 channels?

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Grunnet, Morten; Rasmussen, Hanne B

    2006-01-01

    The corticosteroid hormone induced factor (CHIF) is a member of the one-transmembrane segment protein family named FXYD, which also counts phospholemman and the Na,K-pump gamma-subunit. Originally it was suggested that CHIF could induce the expression of the I(Ks) current when expressed in Xenopu...

  3. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

  4. Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor.

    Science.gov (United States)

    Oh, J D; Butcher, L L; Woolf, N J

    1991-04-24

    Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 microgram/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eight postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic

  5. Selective thyroid hormone receptor modulators

    Directory of Open Access Journals (Sweden)

    Girish Raparti

    2013-01-01

    Full Text Available Thyroid hormone (TH is known to have many beneficial effects on vital organs, but its extrapolation to be used therapeutically has been restricted by the fact that it does have concurrent adverse effects. Recent finding of various thyroid hormone receptors (TR isoforms and their differential pattern of tissue distribution has regained interest in possible use of TH analogues in therapeutics. These findings were followed by search of compounds with isoform-specific or tissue-specific action on TR. Studying the structure-activity relationship of TR led to the development of compounds like GC1 and KB141, which preferentially act on the β1 isoform of TR. More recently, eprotirome was developed and has been studied in humans. It has shown to be effective in dyslipidemia by the lipid-lowering action of TH in the liver and also in obesity. Another compound, 3,5-diiodothyropropionic acid (DITPA, binds to both α- and β-type TRs with relatively low affinity and has been shown to be effective in heart failure (HF. In postinfarction models of HF and in a pilot clinical study, DITPA increased cardiac performance without affecting the heart rate. TR antagonists like NH3 can be used in thyrotoxicosis and cardiac arrhythmias. However, further larger clinical trials on some of these promising compounds and development of newer compounds with increased selectivity is required to achieve higher precision of action and avoid adverse effects seen with TH.

  6. Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

    Science.gov (United States)

    Inukai, T; Takanashi, K; Takebayashi, K; Fujiwara, Y; Tayama, K; Takemura, Y

    1999-10-01

    The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, Phyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (Phormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

  7. Sex hormones in the modulation of irritable bowel syndrome.

    Science.gov (United States)

    Mulak, Agata; Taché, Yvette; Larauche, Muriel

    2014-03-14

    Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.

  8. Sex hormonal modulation of interhemispheric transfer time.

    Science.gov (United States)

    Hausmann, M; Hamm, J P; Waldie, K E; Kirk, I J

    2013-08-01

    It is still a matter of debate whether functional cerebral asymmetries (FCA) of many cognitive processes are more pronounced in men than in women. Some evidence suggests that the apparent reduction in women's FCA is a result of the fluctuating levels of gonadal steroid hormones over the course of the menstrual cycle, making their FCA less static than for men. The degree of lateralization has been suggested to depend on interhemispheric communication that may be modulated by gonadal steroid hormones. Here, we employed visual-evoked EEG potentials to obtain a direct measure of interhemispheric communication during different phases of the menstrual cycle. The interhemispheric transfer time (IHTT) was estimated from the interhemispheric latency difference of the N170 component of the visual-evoked potential from either left or right visual field presentation. Nineteen right-handed women with regular menstrual cycles were tested twice, once during the menstrual phase, when progesterone and estradiol levels are low, and once during the luteal phase when progesterone and estradiol levels are high. Plasma steroid levels were determined by blood-based immunoassay at each session. It was found that IHTT, in particular from right-to-left, was generally longer during the luteal phase relative to the menstrual phase. This effect occurred as a consequence of a slowed absolute N170 latency of the indirect pathway (i.e. left hemispheric response after LVF stimulation) and, in particular, a shortened latency of the direct pathway (i.e. right hemispheric response after LVF stimulation) during the luteal phase. These results show that cycle-related effects are not restricted to modulation of processes between hemispheres but also apply to cortical interactions, especially within the right hemisphere. The findings support the view that plastic changes in the female brain occur during relatively short-term periods across the menstrual cycle. Copyright © 2013 Elsevier Ltd. All rights

  9. Taste perception, associated hormonal modulation, and nutrient intake

    Science.gov (United States)

    Loper, Hillary B.; La Sala, Michael; Dotson, Cedrick

    2015-01-01

    It is well known that taste perception influences food intake. After ingestion, gustatory receptors relay sensory signals to the brain, which segregates, evaluates, and distinguishes the stimuli, leading to the experience known as “flavor.” It is well accepted that five taste qualities – sweet, salty, bitter, sour, and umami – can be perceived by animals. In this review, the anatomy and physiology of human taste buds, the hormonal modulation of taste function, the importance of genetic chemosensory variation, and the influence of gustatory functioning on macronutrient selection and eating behavior are discussed. Individual genotypic variation results in specific phenotypes of food preference and nutrient intake. Understanding the role of taste in food selection and ingestive behavior is important for expanding our understanding of the factors involved in body weight maintenance and the risk of chronic diseases including obesity, atherosclerosis, cancer, diabetes, liver disease, and hypertension. PMID:26024495

  10. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    Science.gov (United States)

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  11. Role of insulin hormone in modulation of inflammatory phenomena

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2011-09-01

    Full Text Available Evidence demonstrates the involvement of hormones in thedevelopment of inflammatory response. Inflammation evokes markedstructural alterations of microvasculature, besides migration ofleukocytes from microcirculation to the site of lesion. These alterations are caused primarily by release or activation of endogenous mediators, in which hormones play an integral role in this regulatory system. Binding sites for many hormones may be characterized by vascular structures and hematogenous cells involved with the inflammatory response. Quantitative alterations of inflammatory events involving the decrease in microvascular response to inflammatory mediators, deficiency in the leukocyte-endothelium interaction, reduction of cell concentration in the inflammatory exudate, and failure of the phagocyte function of mononuclear cells were observed in insulindeficient states. Therefore, inflammation is not merely a local response, but rather a process controlled by hormones in which insulin plays an essential role in modulation of these phenomena, and assures tissue repair and remodeling within the limits of normality.

  12. Fibroblast growth factor 23 - et fosfatregulerende hormon

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe; Pedersen, Susanne Møller; Kassem, Moustapha

    2010-01-01

    Fibroblast growth factor 23 (FGF23) er et nyligt identificeret fosfatonin. FGF23's fysiologiske hovedfunktion er at opretholde normalt serumfosfat og at virke som et D-vitaminmodregulatorisk hormon. Sygdomme, der er koblet til forhøjet serum FGF23, er hypofosfatæmisk rakitis, fibrøs dysplasi og t...

  13. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Cannell, Elizabeth; Dornan, Anthony J.; Halberg, Kenneth Agerlin

    2016-01-01

    Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin...

  14. The Role of Steroid Hormones on the Modulation of Neuroinflammation by Dietary Interventions

    Directory of Open Access Journals (Sweden)

    Andrea Rodrigues Vasconcelos

    2016-02-01

    Full Text Available Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain.The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer´s and Parkinson´s diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, whilst metabolic syndromes, like diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact on the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, like calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

  15. Modulation of taste responsiveness by the satiation hormone peptide YY

    Science.gov (United States)

    La Sala, Michael S.; Hurtado, Maria D.; Brown, Alicia R.; Bohórquez, Diego V.; Liddle, Rodger A.; Herzog, Herbert; Zolotukhin, Sergei; Dotson, Cedrick D.

    2013-01-01

    It has been hypothesized that the peripheral taste system may be modulated in the context of an animal's metabolic state. One purported mechanism for this phenomenon is that circulating gastrointestinal peptides modulate the functioning of the peripheral gustatory system. Recent evidence suggests endocrine signaling in the oral cavity can influence food intake (FI) and satiety. We hypothesized that these hormones may be affecting FI by influencing taste perception. We used immunohistochemistry along with genetic knockout models and the specific reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to identify a role for PYY signaling in taste. We show that PYY is expressed in subsets of taste cells in murine taste buds. We also show, using brief-access testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter-tasting stimuli, as well as to lipid emulsions. We show that salivary PYY augmentation, via viral vector therapy, rescues behavioral responsiveness to a lipid emulsion but not to bitter stimuli and that this response is likely mediated via activation of Y2 receptors localized apically in taste cells. Our findings suggest distinct functions for PYY produced locally in taste cells vs. that circulating systemically.—La Sala, M. S., Hurtado, M. D., Brown, A. R., Bohórquez, D. V., Liddle, R. A., Herzog, H., Zolotukhin, S., Dotson, C. D. Modulation of taste responsiveness by the satiation hormone peptide YY. PMID:24043261

  16. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

    Science.gov (United States)

    Cannell, Elizabeth; Dornan, Anthony J; Halberg, Kenneth A; Terhzaz, Selim; Dow, Julian A T; Davies, Shireen-A

    2016-06-01

    Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Menopause, hormone replacement and RR and QT modulation during sleep

    Czech Academy of Sciences Publication Activity Database

    Lanfranchi, P. A.; Gosselin, N.; Kára, T.; Jurák, Pavel; Somers, V. K.; Denesle, R.; Petit, D.; Carrier, J.; Nadeau, R.; Montplaisir, J.

    2005-01-01

    Roč. 6, č. 6 (2005), s. 561-566 ISSN 1389-9457 R&D Projects: GA ČR(CZ) GA102/05/0402 Keywords : Sleep * Menopause * RR interval * QT interval * Gender * Hormones Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 2.711, year: 2005

  18. Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

    Science.gov (United States)

    Cornell, R P; McClellan, C C

    1982-12-01

    Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.

  19. Hormones and growth factors in breast cancer

    African Journals Online (AJOL)

    Herman-Giddens M. Condylomata acuminata in children and sexual abuse. Genitourin ..... accommodated reasonably easily in the outline of hormone action referred to ... tumours may still respond to hormone manipulation with another type of ...

  20. Adrenal-derived stress hormones modulate ozone-induced ...

    Science.gov (United States)

    Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED)or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effect of acute ozone exposure. To understand the influence of adrenal-derived stress hormones in mediating ozone-induced lung injury/inflammation, we assessed global gene expression (mRNA sequencing) and selected proteins in lung tissues from male Wistar-Kyoto rats that underwent DEMED, ADREX, or sham surgery (SHAM)prior to their exposure to air or ozone (1 ppm),4 h/day for 1 or 2days. Ozone exposure significantly changed the expression of over 2300 genes in lungs of SHAM rats, and these changes were markedly reduced in DEMED and ADREX rats. SHAM surgery but not DEMED or ADREX resulted in activation of multiple ozone-responsive pathways, including glucocorticoid, acute phase response, NRF2, and Pl3K-AKT.Predicted targets from sequencing data showed a similarity between transcriptional changes induced by ozone and adrenergic and steroidal modulation of effects in SHAM but not ADREX rats. Ozone-induced Increases in lung 116 in SHAM rats coincided with neutrophilic Inflammation, but were diminished in DEMED and ADREX rats. Although ozone exposure in SHAM rats did not significantly alter mRNA expression of lfny and 11-4, the IL-4 protein and ratio of IL-4 to IFNy (IL-4/IFNy) proteins increased suggesting a tendency for a Th2 response. This did not occur

  1. Sexual hormones modulate compensatory renal growth and function

    Directory of Open Access Journals (Sweden)

    Pablo J. Azurmendi

    2013-12-01

    Full Text Available The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG that follows uninephrectomy (uNx is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50% while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  2. A selective androgen receptor modulator for hormonal male contraception.

    Science.gov (United States)

    Chen, Jiyun; Hwang, Dong Jin; Bohl, Casey E; Miller, Duane D; Dalton, James T

    2005-02-01

    The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide (C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (K(i) = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The doses required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to half the size of the maximum effects (i.e., ED(50)) were 0.78 +/- 0.06, 0.88 +/- 0.1, and 0.17 +/- 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone concentration in intact rats after 2 weeks of treatment. Marked suppression of spermatogenesis was observed after 10 weeks of treatment with C-6 in intact male rats. Pharmacokinetic studies of C-6 in male rats revealed that C-6 was well absorbed after oral administration (bioavailability 76%), with a long (6.3 h) half-life at a dose of 10 mg/kg. These studies show that C-6 mimicked the in vivo pharmacologic and endocrine effects of testosterone while maintaining the oral bioavailability and tissue-selective actions of nonsteroidal SARMs.

  3. Hormones in pain modulation and their clinical implications for pain control: a critical review.

    Science.gov (United States)

    Chen, Xueyin; Zhang, Jinyuan; Wang, Xiangrui

    2016-07-01

    Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.

  4. Reproductive and hormonal factors in male and female colon cancer

    NARCIS (Netherlands)

    Kampman, E.; Bijl, A.J.; Kok, C.; Veer, P. van 't

    1994-01-01

    We analysed data from a case-control study in the Netherlands in order to investigate whether reproductive events and hormonal factors are similarly related to colon cancer risk in men and women after adjustment for dietary factors. In total, 232 colon cancer cases (102 women, 130 men) and 259

  5. Anthropometric and hormonal risk factors for male breast cancer

    DEFF Research Database (Denmark)

    Brinton, Louise A; Cook, Michael B; McCormack, Valerie

    2014-01-01

    BACKGROUND: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. METHODS: In the Male Breast Cancer Pooling Project, a consorti...

  6. Growth hormone, growth factors, and acromegaly

    Energy Technology Data Exchange (ETDEWEB)

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  7. Thyroid hormone: the modulator of erectile function in the rabbit ...

    African Journals Online (AJOL)

    The possible role of thyroid hormones in the Nitric Oxide (NO)- mediated response to sexual stimulation, and on prostaglandin E1 (PGE1) and Sildenafil in the treatment of erectile dysfunction was investigated using the corpus cavernosum of the New Zealand rabbit animal model. The parameters studied were penile ...

  8. Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.

    Science.gov (United States)

    Devadas, Krishnakumar; Biswas, Santanu; Ragupathy, Viswanath; Lee, Sherwin; Dayton, Andrew; Hewlett, Indira

    2018-01-01

    Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.

  9. Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

    OpenAIRE

    Kelly, K L; Gutierrez, G; Martin, A

    1988-01-01

    The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine,...

  10. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  11. Hypoxia-Related Hormonal Appetite Modulation in Humans during Rest and Exercise: Mini Review

    Directory of Open Access Journals (Sweden)

    Tadej Debevec

    2017-05-01

    Full Text Available Obesity is associated with numerous chronic ailments and represents one of the major health and economic issues in the modernized societies. Accordingly, there is an obvious need for novel treatment approaches. Recently, based on the reports of reduced appetite and subsequent weight loss following high-altitude sojourns, exposure to hypoxia has been proposed as a viable weight-reduction strategy. While altitude-related appetite modulation is complex and not entirely clear, hypoxia-induced alterations in hormonal appetite modulation might be among the key underlying mechanisms. The present paper summarizes the up-to-date research on hypoxia/altitude-induced changes in the gut and adipose tissue derived peptides related to appetite regulation. Orexigenic hormone ghrelin and anorexigenic peptides leptin, glucagon-like peptide-1, peptide YY, and cholecystokinin have to-date been investigated as potential modulators of hypoxia-driven appetite alterations. Current evidence suggests that hypoxia can, especially acutely, lead to decreased appetite, most probably via reduction of acylated ghrelin concentration. Hypoxia-related short and long-term changes in other hormonal markers are more unclear although hypoxia seems to importantly modulate leptin levels, especially following prolonged hypoxic exposures. Limited evidence also suggests that different activity levels during exposures to hypoxia do not additively affect hormonal appetite markers. Although very few studies have been performed in obese/overweight individuals, the available data indicate that hypoxia/altitude exposures do not seem to differentially affect appetite regulation via hormonal pathways in this cohort. Given the lack of experimental data, future well-controlled acute and prolonged studies are warranted to expand our understanding of hypoxia-induced hormonal appetite modulation and its kinetics in health and disease.

  12. Adrenal-derived stress hormones modulate ozone-induced lung injury and inflammation

    Science.gov (United States)

    Ozone-induced systemic effects are modulated through activation of the neuro-hormonal stress response pathway. Adrenal demedullation (DEMED)or bilateral total adrenalectomy (ADREX) inhibits systemic and pulmonary effect of acute ozone exposure. To understand the influence of adre...

  13. Thyroid hormone modulates the extracellular matrix organization and expression in cerebellar astrocyte: effects on astrocyte adhesion.

    Science.gov (United States)

    Trentin, Andréa Gonçalves; De Aguiar, Cláudia Beatriz Nedel Mendes; Garcez, Ricardo Castilho; Alvarez-Silva, Marcio

    2003-06-01

    The effects of thyroid hormone (T(3)) on extracellular matrix (ECM) expression and organization in cerebellar astrocytes were studied. Control astrocytes exhibit laminin immunostaining distributed in a punctate configuration and fibronectin concentrated in focal points at the cell surface. These cells attach to the substratum by membrane points, as shown by scanning microscopy, possibly by focal points stained to fibronectin. In contrast, after T(3) treatment, laminin assumes a fibrillary pattern and fibronectin becomes organized in filaments homogeneously distributed on the cell surface; the cells acquire a very flat and spread morphology. T(3) treatment also modulates astrocyte adhesion. In addition, increased expression of both laminin and fibronectin was detected by Western blot. These alterations in fibronectin and/or laminin production and organization may be involved in the flat and spread morphology and in altered adhesion. We observed that fibroblast growth factor-2 (FGF(2)) added to cultures had similar effects to those described to T(3). Neutralizing antibodies against FGF(2) reversed T(3) effects on fibronectin and laminin distribution. We also observed that cerebellar neurons co-cultured on T(3)-treated astrocytes had an increase in the number of cells and presented longer neurites. Thus, we propose a novel mechanism of the effect of thyroid hormone on cerebellar development mediated by astrocytes: T(3) may induce astrocyte secretion of growth factors, mainly FGF(2), that autocrinally stimulate astrocyte proliferation, reorganization in ECM proteins, and alterations in cell spreading and adhesion. These effects may indirectly influence neuronal development. Copyright 2003 Wiley-Liss, Inc.

  14. The Role of Steroid Hormones on the Modulation of Neuroinflammation by Dietary Interventions

    OpenAIRE

    Andrea Rodrigues Vasconcelos; João Victor eCabral-Costa; Caio Henrique Mazucanti; Cristoforo eScavone; Elisa Mitiko Kawamoto

    2016-01-01

    Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain.The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role ...

  15. Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

    Science.gov (United States)

    Kelly, K L; Gutierrez, G; Martin, A

    1988-01-01

    The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine, which was both time- and dose-dependent. The stimulatory effect of isoprenaline was inhibited in a dose-dependent manner by oxytocin or insulin. Oxytocin inhibited the incorporation of [Me-3H]choline into phosphatidylcholine in both the presence and the absence of isoprenaline, whereas in the absence of isoprenaline insulin increased the incorporation of [Me-3H]choline into phosphatidylcholine. The effects of isoprenaline, oxytocin and insulin on the incorporation of [3H]choline into phosphatidylcholine were paralleled by changes in the activity of CTP:phosphocholine cytidylyltransferase. PMID:2849424

  16. Women's hormone levels modulate the motivational salience of facial attractiveness and sexual dimorphism.

    Science.gov (United States)

    Wang, Hongyi; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Jones, Benedict C

    2014-12-01

    The physical attractiveness of faces is positively correlated with both behavioral and neural measures of their motivational salience. Although previous work suggests that hormone levels modulate women's perceptions of others' facial attractiveness, studies have not yet investigated whether hormone levels also modulate the motivational salience of facial characteristics. To address this issue, we investigated the relationships between within-subject changes in women's salivary hormone levels (estradiol, progesterone, testosterone, and estradiol-to-progesterone ratio) and within-subject changes in the motivational salience of attractiveness and sexual dimorphism in male and female faces. The motivational salience of physically attractive faces in general and feminine female faces, but not masculine male faces, was greater in test sessions where women had high testosterone levels. Additionally, the reward value of sexually dimorphic faces in general and attractive female faces, but not attractive male faces, was greater in test sessions where women had high estradiol-to-progesterone ratios. These results provide the first evidence that the motivational salience of facial attractiveness and sexual dimorphism is modulated by within-woman changes in hormone levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses

    DEFF Research Database (Denmark)

    LeBlanc, Sacha; Höglund, Erik; Gilmour, Kathleen M.

    2012-01-01

    shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout....... We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response...

  18. Factors That Modulate Neurogenesis: A Top-Down Approach.

    Science.gov (United States)

    LaDage, Lara D

    2016-08-24

    Although hippocampal neurogenesis in the adult brain has been conserved across the vertebrate lineage, laboratory studies have primarily examined this phenomenon in rodent models. This approach has been successful in elucidating important factors and mechanisms that can modulate rates of hippocampal neurogenesis, including hormones, environmental complexity, learning and memory, motor stimulation, and stress. However, recent studies have found that neurobiological research on neurogenesis in rodents may not easily translate to, or explain, neurogenesis patterns in nonrodent systems, particularly in species examined in the field. This review examines some of the evolutionary and ecological variables that may also modulate neurogenesis patterns. This 'top-down' and more naturalistic approach, which incorporates ecology and natural history, particularly of nonmodel species, may allow for a more comprehensive understanding of the functional significance of neurogenesis. © 2016 S. Karger AG, Basel.

  19. Hormonal, anthropometric and lipid factors associated with idiopathic pubertal gynecomastia.

    Science.gov (United States)

    Al Alwan, Ibrahim; Al Azkawi, Hanan; Badri, Motasim; Tamim, Hani; Al Dubayee, Mohammed; Tamimi, Waleed

    2013-01-01

    To determine factors associated with pubertal gynecomastia. A cross-sectional study among healthy male school children and adolescents in Riyadh, Saudi Arabia. Subjects were selected from diverse socioeconomic backgrounds. Tanner stage, height, weight, blood hormonal levels (leutilizing hormone [LH], follicle-stimulating hormone [FSH], total testosterone, and estradiol), and anthropometric and lipid parameters (body mass index [BMI], triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), were collected and compared in children with and without gynecomastia. The study included 542 children and adolescents. Median (interquartile range) age in the whole group was 11(8-13) years. The prevalence of gynecomastia was 185/542 (34%), with a peak at age 14. The 2 groups compared had nonsignificant difference in cholesterol (P=.331), LH (P=.215) and FSH (P=.571) levels. Those with gynecomastia were significantly older, had lower gonad stage, had higher anthropometric (height, weight, and BMI), and lipid (triglycerides, HDL, and LDL) values. In multivariate regression analysis, factors significantly associated with gynecomastia were BMI (odds ratio [OR]=1.05; 95%CI 1.00-1.10; P=.013), HDL (OR=0.42; 95%CI 0.19-0.92; P=.03), and gonad (Stage II OR=2.23; 95%CI 1.27-3.92; P=.005, Stage III OR=6.40; 95%CI 2.70-15.0; P gynecomastia tends to increase in mid-puberty. In our setting, BMI, HDL, and gonad stage were the major factors associated with the development of pubertal gynecomastia.

  20. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-01-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation

  1. Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies

    NARCIS (Netherlands)

    Key, T. J.; Appleby, P. N.; Reeves, G. K.; Roddam, A. W.; Helzlsouer, K. J.; Alberg, A. J.; Rollison, D. E.; Dorgan, J. F.; Brinton, L. A.; Overvad, K.; Kaaks, R.; Trichopoulou, A.; Clavel-Chapelon, F.; Panico, S.; Duell, E. J.; Peeters, P. H. M.; Rinaldi, S.; Riboli, E.; Fentiman, I. S.; Dowsett, M.; Manjer, J.; Lenner, P.; Hallmans, G.; Baglietto, L.; English, D. R.; Giles, G. G.; Hopper, J. L.; Severi, G.; Morris, H. A.; Koenig, K.; Zeleniuch-Jacquotte, A.; Arslan, A. A.; Toniolo, P.; Shore, R. E.; Krogh, V.; Micheli, A.; Berrino, F.; Muti, P.; Barrett-Connor, E.; Laughlin, G. A.; Kabuto, M.; Akiba, S.; Stevens, R. G.; Neriishi, K.; Land, C. E.; Cauley, J. A.; Lui, Li Yung; Cummings, Steven R.; Gunter, M. J.; Rohan, T. E.

    2011-01-01

    BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone

  2. Structural Basis for Prereceptor Modulation of Plant Hormones by GH3 Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, Corey S.; Zubieta, Chloe; Herrmann, Jonathan; Kapp, Ulrike; Nanao, Max H.; Jez, Joseph M. (WU); (EMBL); (ESRF)

    2013-04-08

    Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators of plant hormone action; however, the molecular basis for their hormone selectivity is unclear. Here, we report the crystal structures of benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features for the conjugation of amino acids to diverse acyl acid substrates and highlight the importance of conformational changes in the carboxyl-terminal domain for catalysis. We also identify residues forming the acyl acid binding site across the GH3 family and residues critical for amino acid recognition. Our results demonstrate how a highly adaptable three-dimensional scaffold is used for the evolution of promiscuous activity across an enzyme family for modulation of plant signaling molecules.

  3. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

    Science.gov (United States)

    Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

    2013-11-01

    Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.

  4. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Science.gov (United States)

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  5. Force Factor Modulation in Electro Dynamic Loudspeakers

    DEFF Research Database (Denmark)

    Risbo, Lars; Agerkvist, Finn T.; Tinggaard, Carsten

    2016-01-01

    The relationship between the non-linear phenomenon of ’reluctance force’ and the position dependency of the voice coil inductance was established in 1949 by Cunningham, who called it ’magnetic attraction force’. This paper revisits Cunningham’s analysis and expands it into a generalised form...... that includes the frequency dependency and applies to coils with non-inductive (lossy) blocked impedance. The paper also demonstrates that Cunningham’s force can be explained physically as a modulation of the force factor which again is directly linked to modulation of the flux of the coil. A verification based...... on both experiments and simulations is presented along discussions of the impact of force factor modulation for various motor topologies. Finally, it is shown that the popular L2R2 coil impedance model does not correctly predict the force unless the new analysis is applied....

  6. [Hormonal and inflammatory impact of different dietetic composition: emphasis on dietary patterns and specific dietary factors].

    Science.gov (United States)

    Bressan, Josefina; Hermsdorff, Helen H M; Zulet, María Angeles; Martínez, José Alfredo

    2009-07-01

    Healthy dietary pattern, characterized by the consumption of fruits, vegetables, white meats, skim dairy products, nuts and moderate intake of vegetable oils and alcohol, is an important factor for a lower risk of chronic disease such as obesity, metabolic syndrome and cardiovascular disease. This beneficial effect can be explained, at least partially, by its modulating role on biomarkers of insulin sensitivity and atherosclerosis as well as of inflammation and endothelial function. On the other hand, the intake of specific dietary factors, such as unsaturated fatty acids (oleic and alpha-linolenic) and micronutrients with antioxidant properties (vitamins A, E and C; selenium, zinc) has been discussed, due to its potential protector action due to chronic disease occurrence and its possible profits in hormonal, metabolic and inflammatory regulations that these dietetic factors can provide within a nutritional treatment to obesity and metabolic syndrome.

  7. MRI of growth hormone-secreting pituitary adenomas: factors determining pretreatment hormone levels

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, N.; Iuchi, T.; Eda, M.; Yamaura, A. [Dept. of Neurological Surgery, Chiba University School of Medicine (Japan); Isono, S. [Dept. of Neurological Surgery, Anesthesiology, Chiba University School of Medicine, Chiba (Japan)

    1999-10-01

    Preoperative serum growth hormone (GH) level is one of the most important determinants of outcome. Our aim was to assess MRI findings which may correlate with pretreatment GH levels in GH-secreting adenomas. We retrospectively studied 29 patients with acromegaly caused by a pituitary adenoma. Tumor size (height, width, thickness and volume), suprasellar extension, sphenoid or cavernous sinus invasion, signal intensity and contrast enhancement were studied. Linear regression analysis or Fisher's exact probability test was used for statistical analysis. Factors related to high GH levels were the maximum dimension of the tumour (r = 0.496, P < 0.01), its volume (r = 0.439, P < 0.05), spenoid sinus invasion (P < 0.01) and intracavernous carotid artery encasement (P < 0.01). The other items were not related to serum GH levels. Since we believe surgery is the first choice of treatment and the cavernous sinus is difficult of access with a conventional surgical approach, preoperative assessment of invasion into the cavernous sinus is critical for predicting the surgical outcome. Low GH levels (5-50 ng/ml) were found with tumours medial to the intercarotid line and high levels (more than 101 ng/ml) with invasive tumours with carotid artery encasement. Variable GH levels were noted with tumours extending beyond the intercarotid line. Because functioning adenomas invading the cavernous sinus tend to have markedly high hormone levels, and only patients with carotid artery encasement showed markedly elevated GH levels, we believe carotid artery encasement a reliable MRI indicator of cavernous sinus invasion. (orig.)

  8. Identification of a novel modulator of thyroid hormone receptor-mediated action.

    Directory of Open Access Journals (Sweden)

    Bernhard G Baumgartner

    Full Text Available BACKGROUND: Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. METHODOLOGY/PRINCIPAL FINDINGS: We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TR(alpha1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR( alpha1 and to T(3-responsive promoters, as shown by ChIP assays. T(3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. CONCLUSIONS/SIGNIFICANCE: Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease.

  9. Melanin-concentrating hormone (MCH: a new sleep factor?

    Directory of Open Access Journals (Sweden)

    Pablo eTorterolo

    2011-03-01

    Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

  10. Transgenerational Social Stress, Immune Factors, Hormones, and Social Behavior

    Directory of Open Access Journals (Sweden)

    Christopher Anthony Murgatroyd

    2016-01-01

    Full Text Available A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior. The exposure of maternal rats to the chronic social stress (CSS of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP and intercellular adhesion molecule-1 (ICAM-1 in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1, and vascular endothelial growth factor (VEGF. Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH was increased in F2 males, and brain-derived neurotrophic factor (BDNF was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and

  11. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

    Science.gov (United States)

    Bortvedt, Sarah F; Lund, P Kay

    2012-03-01

    To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

  12. The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

    Directory of Open Access Journals (Sweden)

    Oliver eRawashdeh

    2012-03-01

    Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

  13. Thyroid hormone modulates food intake and glycemia via ghrelin secretion in Zucker fatty rats.

    Science.gov (United States)

    Patel, K; Joharapurkar, A; Dhanesha, N; Patel, V; Kshirsagar, S; Raval, P; Raval, S; Jain, M R

    2014-10-01

    Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones. © Georg Thieme Verlag KG Stuttgart · New York.

  14. DAT1-Genotype and Menstrual Cycle, but Not Hormonal Contraception, Modulate Reinforcement Learning: Preliminary Evidence.

    Science.gov (United States)

    Jakob, Kristina; Ehrentreich, Hanna; Holtfrerich, Sarah K C; Reimers, Luise; Diekhof, Esther K

    2018-01-01

    Hormone by genotype interactions have been widely ignored by cognitive neuroscience. Yet, the dependence of cognitive performance on both baseline dopamine (DA) and current 17ß-estradiol (E2) level argues for their combined effect also in the context of reinforcement learning. Here, we assessed how the interaction between the natural rise of E2 in the late follicular phase (FP) and the 40 base-pair variable number tandem repeat polymorphism of the dopamine transporter (DAT1) affects reinforcement learning capacity. 30 women with a regular menstrual cycle performed a probabilistic feedback learning task twice during the early and late FP. In addition, 39 women, who took hormonal contraceptives (HC) to suppress natural ovulation, were tested during the "pill break" and the intake phase of HC. The present data show that DAT1-genotype may interact with transient hormonal state, but only in women with a natural menstrual cycle. We found that carriers of the 9-repeat allele (9RP) experienced a significant decrease in the ability to avoid punishment from early to late FP. Neither homozygote subjects of the 10RP allele, nor subjects from the HC group showed a change in behavior between phases. These data are consistent with neurobiological studies that found that rising E2 may reverse DA transporter function and could enhance DA efflux, which would in turn reduce punishment sensitivity particularly in subjects with a higher transporter density to begin with. Taken together, the present results, although based on a small sample, add to the growing understanding of the complex interplay between different physiological modulators of dopaminergic transmission. They may not only point out the necessity to control for hormonal state in behavioral genetic research, but may offer new starting points for studies in clinical settings.

  15. DAT1-Genotype and Menstrual Cycle, but Not Hormonal Contraception, Modulate Reinforcement Learning: Preliminary Evidence

    Directory of Open Access Journals (Sweden)

    Kristina Jakob

    2018-02-01

    Full Text Available Hormone by genotype interactions have been widely ignored by cognitive neuroscience. Yet, the dependence of cognitive performance on both baseline dopamine (DA and current 17ß-estradiol (E2 level argues for their combined effect also in the context of reinforcement learning. Here, we assessed how the interaction between the natural rise of E2 in the late follicular phase (FP and the 40 base-pair variable number tandem repeat polymorphism of the dopamine transporter (DAT1 affects reinforcement learning capacity. 30 women with a regular menstrual cycle performed a probabilistic feedback learning task twice during the early and late FP. In addition, 39 women, who took hormonal contraceptives (HC to suppress natural ovulation, were tested during the “pill break” and the intake phase of HC. The present data show that DAT1-genotype may interact with transient hormonal state, but only in women with a natural menstrual cycle. We found that carriers of the 9-repeat allele (9RP experienced a significant decrease in the ability to avoid punishment from early to late FP. Neither homozygote subjects of the 10RP allele, nor subjects from the HC group showed a change in behavior between phases. These data are consistent with neurobiological studies that found that rising E2 may reverse DA transporter function and could enhance DA efflux, which would in turn reduce punishment sensitivity particularly in subjects with a higher transporter density to begin with. Taken together, the present results, although based on a small sample, add to the growing understanding of the complex interplay between different physiological modulators of dopaminergic transmission. They may not only point out the necessity to control for hormonal state in behavioral genetic research, but may offer new starting points for studies in clinical settings.

  16. Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Genazzani, Alessandro D; Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Santagni, Susanna; Rattighieri, Erica; Ricchieri, Federica; Chierchia, Elisa; Simoncini, Tommaso

    2012-02-01

    To evaluate the influence of estriol administration on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study. Patients with FHA in a clinical research environment. Twelve hypogonadotropic patients affected by FHA. Pulsatility study of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and a gonadotropin-releasing hormone (GnRH) test (10 μg in bolus) at baseline condition and after 8 weeks of therapy with 2 mg/day of estriol. Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17α-hydroxyprogesterone (17-OHP), cortisol, androstenedione (A), testosterone (T), thyroid-stimulating hormone (TSH), free triiodothyronine (fT(3)), free thyroxine (fT(4)), and insulin, and pulse detection. After treatment, the FHA patients showed a statistically significant increase of LH plasma levels (from 0.7 ± 0.1 mIU/mL to 3.5 ± 0.3 mIU/mL) and a statistically significant increase of LH pulse amplitude with no changes in LH pulse frequency. In addition, the LH response to the GnRH bolus was a statistically significant increase. Estriol administration induced the increase of LH plasma levels in FHA and improved GnRH-induced LH secretion. These findings suggest that estriol administration modulates the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of LH synthesis and secretion in hypogonadotropic patients with FHA. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. The role of hormones and growth factors in the cellular proliferation control in mammals

    International Nuclear Information System (INIS)

    Armelin, H.A.

    1978-01-01

    A review is done about fibroblast proliferation, its control by classic hormones and hormonal growth factors, showing their main implications and the stage of this research at present. The control exerted on fibronlast proliferation by hormonal growth factors and classic hormones is demonstrated. The existence of basic mechanisms valid for all types of cells is suggested. Experiences are carried out with the aim of finding growth mutants useful in the elucidation of the biochemical mechanisms involved in growth regulation. Radiactive precursors and autoradiographic techniques are used in the research. (M.A.) [pt

  18. Transcriptional regulation by competing transcription factor modules.

    Directory of Open Access Journals (Sweden)

    Rutger Hermsen

    2006-12-01

    Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

  19. Modulation of transcription factors by curcumin.

    Science.gov (United States)

    Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

    2007-01-01

    Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

  20. Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Malemud Charles J

    2004-10-01

    Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

  1. Modulation of gene expression by nutritional state and hormones in Bombyx larvae in relation to its growth period.

    Science.gov (United States)

    Thounaojam, Bembem; Keshan, Bela

    2017-11-01

    Insect growth and development are mainly regulated via synchronization of many extrinsic and intrinsic factors such as nutrition and hormones. Previously we have demonstrated that larval growth period influences the effect of insulin on the accumulation of glycogen in the fat body of Bombyx larvae. In the present study we demonstrate that Bombyx larvae at the terminal growth period (TGP, after critical weight) had a significantly greater increase in the expression level of Akt in the fat body than at the active growth period (AGP, before critical weight). The larvae at TGP also showed an increase in the expression level of ecdysone receptors (EcRB1 and USP1) and ecdysone-induced early genes (E75A and broad). The treatment of bovine insulin and methoprene to larvae at AGP induced the transcript levels of Akt, irrespective of the nutritional status of the larvae. However, in larvae at TGP, insulin repressed the transcript level of Akt. On contrary, 20-hydroxyecdysone (20E) induced the expression level of Akt in TGP larvae, but at feeding only. Insulin and 20E thus showed an antagonistic action on the Akt expression level in TGP larvae under feeding. The studies thus showed that larval growth period influences the expression level of Akt and ecdysone receptors in Bombyx. Further, the growth period and nutrition modulate the effect of exogenous hormones on Akt expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Maternal hormonal interventions as a risk factor for Autism Spectrum ...

    Indian Academy of Sciences (India)

    2013-11-05

    Nov 5, 2013 ... children (471 ASD and 471 controls) across 9 cities in India participated in the .... Gender characteristics of children born to mothers who have undergone .... McEwen BS 1987 Steroid hormones and brain development: some.

  3. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

    Science.gov (United States)

    Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

    2011-01-01

    Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

  4. Pituitary transcription factors in the aetiology of combined pituitary hormone deficiency.

    Science.gov (United States)

    Pfäffle, R; Klammt, J

    2011-02-01

    The somatotropic axis is the central postnatal regulator of longitudinal growth. One of its major components--growth hormone--is produced by the anterior lobe of the pituitary, which also expresses and secretes five additional hormones (prolactin, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone, adrenocorticotropic hormone). Proper development of the pituitary assures the regulation of critical processes such as metabolic control, puberty and reproduction, stress response and lactation. Ontogeny of the adenohypophysis is orchestrated by inputs from neighbouring tissues, cellular signalling molecules and transcription factors. Perturbation of expression or function of these factors has been implicated in the aetiology of combined pituitary hormone deficiency (CPHD). Mutations within the genes encoding for the transcription factors LHX3, LHX4, PROP1, and POU1F1 (PIT1) that act at different stages of pituitary development result in unique patterns of hormonal deficiencies reflecting their differential expression during organogenesis. In the case of LHX3 and LHX4 the phenotype may include extra-pituitary manifestations due to the function of these genes/proteins outside the pituitary gland. The remarkable variability in the clinical presentation of affected patients indicates the influence of the genetic background, environmental factors and possibly stochastic events. However, in the majority of CPHD cases the aetiology of this heterogeneous disease remains unexplained, which further suggests the involvement of additional genes. Identification of these factors might also help to close the gaps in our understanding of pituitary development, maintenance and function. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. The role of the habenula-interpeduncular pathway in modulating levels of circulating adrenal hormones.

    Science.gov (United States)

    Murray, M; Murphy, C A; Ross, L L; Haun, F

    1994-01-01

    The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282-3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2-3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic

  6. A HLA class I cis-regulatory element whose activity can be modulated by hormones.

    Science.gov (United States)

    Sim, B C; Hui, K M

    1994-12-01

    To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

  7. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  8. The association of reproductive and lifestyle factors with a score of multiple endogenous hormones.

    Science.gov (United States)

    Shafrir, Amy L; Zhang, Xuehong; Poole, Elizabeth M; Hankinson, Susan E; Tworoger, Shelley S

    2014-10-01

    We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.

  9. Hormonal Disorders as Significant Pathogenetic Factor of Acne in Women

    Directory of Open Access Journals (Sweden)

    L.O. Naumova

    2014-08-01

    Conclusions. Hormonal study of women with acne should include an assessment of the function of ovaries, adrenal glands, thyroid gland, determination of the level of prolactin in the blood plasma and glycated hemoglobin. Treatment should be aimed at management of hormonal and metabolic disorders, and topical treatment of acne. Before 30 years of age it is important to diagnose polycystic ovary syndrome and late forms of congenital dysfunction of the adrenal glands, after 30 — hyperprolactinemia syndrome, hypothyroidism, diabetes mellitus type 2, and after 40 years acne often manifests on the background of ovarian failure.

  10. CD36 Modulates Fasting and Preabsorptive Hormone and Bile Acid Levels.

    Science.gov (United States)

    Shibao, Cyndya A; Celedonio, Jorge E; Tamboli, Robyn; Sidani, Reem; Love-Gregory, Latisha; Pietka, Terri; Xiong, Yanhua; Wei, Yan; Abumrad, Naji N; Abumrad, Nada A; Flynn, Charles Robb

    2018-05-01

    Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM). Obese African American (AA) women carriers of the G allele of rs3211938 (G/T) and weight-matched noncarriers (T/T) were studied before and after a HFM. Two-center study. Obese AA women. HFM. Early preabsorptive responses (10 minutes) and extended excursions in plasma hormones [C-peptide, insulin, incretins, ghrelin fibroblast growth factor (FGF)19, FGF21], BAs, and serum lipoproteins (chylomicrons, very-low-density lipoprotein) were determined. At fasting, G-allele carriers had significantly reduced cholesterol and glycodeoxycholic acid and consistent but nonsignificant reductions of serum lipoproteins. Levels of GLP-1 and pancreatic polypeptide (PP) were reduced 60% to 70% and those of total BAs were 1.8-fold higher. After the meal, G-allele carriers displayed attenuated early (-10 to 10 minute) responses in insulin, C-peptide, GLP-1, gastric inhibitory peptide, and PP. BAs exhibited divergent trends in G allele carriers vs noncarriers concomitant with differential FGF19 responses. CD36 plays an important role in the preabsorptive hormone and BA responses that coordinate brain and gut regulation of energy metabolism.

  11. Modulation of radiosensitivity by growth factors

    International Nuclear Information System (INIS)

    Paris, F.

    2013-01-01

    The full text of the publication follows. For the past 70 years, radiotherapy protocols were defined to target and kill cancer cells. New research developments showed that the tissue or tumor radiosensitivities might be directly modulated by its own microenvironment. Between all the micro-environmental cells, endothelial cells are playing a unique role due to the need of angio-genesis for tumor genesis and to the microvascular endothelial cell apoptosis involved in acute normal tissue and tumor radiosensitivities. Both endothelial behaviours may be controlled by specific growth factors secreted by tumor cells. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two cytokines involved in angio genesis and endothelial cell survival. Because radiation exposure develops opposite molecular and cellular responses by inhibiting proliferation and by enhancing apoptosis, inhibiting these cytokines has been proposed as a relevant strategy to improve radiotherapy efficiency. Drugs or antibody against VEGF, or other growth factors have been used with success to limit endothelial cell resistance, but also to transiently normalize of blood vessels to improve oxygen distribution into the tumor. However, better characterisation of the role of the cytokines will help to better improve the strategy of the use of their antagonists. We demonstrate that bFGF or sphingosin 1 phosphate (S1P), a lipid endothelial growth factor, protects endothelial cells from radiation stress by inhibiting the pre-mitotic apoptosis through enhancement of pro-survival molecular cascade, such as the Pi3K/AKT pathway, but not post-mitotic death. This discrepancy allowed a specific use of S1P as pharmacological drug protecting quiescent endothelial cells, present in normal tissue blood vessels, but not in proliferating angiogenic blood vessels, majority present in tumor blood vessel. In vivo studies are underway. (author)

  12. The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

    Science.gov (United States)

    Chaieb, Leila; Koyama, Takashi; Sarwar, Prioty; Mirth, Christen K.; Smith, Wendy A.; Suzuki, Yuichiro

    2014-01-01

    Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl knockdown larvae delayed the onset of metamorphosis and led to a prolonged larval stage, indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase 3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae. The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo) were reduced in vvl knockdown larvae in the anterior and posterior halves, respectively, indicating that Vvl might influence ecdysone biosynthesis in both the prothoracic gland and additional endocrine sources. Injection of 20-hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of HR3 although molting was never restored. These findings suggest that Vvl coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to influence molting and the timing of metamorphosis. Thus, in both vertebrates and insects, POU factors modulate the production of major neuroendocrine regulators during sexual maturation. PMID:24945490

  13. Seasonal and hormonal modulation of neurotransmitter systems in the song control circuit.

    Science.gov (United States)

    Ball, Gregory F; Balthazart, Jacques

    2010-03-01

    In the years following the discovery of the song system, it was realized that this specialized circuit controlling learned vocalizations in songbirds (a) constitutes a specific target for sex steroid hormone action and expresses androgen and (for some nuclei) estrogen receptors, (b) exhibits a chemical neuroanatomical pattern consisting in a differential expression of various neuropeptides and neurotransmitters receptors as compared to surrounding structures and (c) shows pronounced seasonal variations in volume and physiology based, at least in the case of HVC, on a seasonal change in neuron recruitment and survival. During the past 30 years numerous studies have investigated how seasonal changes, transduced largely but not exclusively through changes in sex steroid concentrations, affect singing frequency and quality by modulating the structure and activity of the song control circuit. These studies showed that testosterone or its metabolite estradiol, control seasonal variation in singing quality by a direct action on song control nuclei. These studies also gave rise to the hypothesis that the probability of song production in response to a given stimulus (i.e. its motivation) is controlled through effects on the medial preoptic area and on catecholaminergic cell groups that project to song control nuclei. Selective pharmacological manipulations confirmed that the noradrenergic system indeed plays a role in the control of singing behavior. More experimental work is, however, needed to identify specific genes related to neurotransmission that are regulated by steroids in functionally defined brain areas to enhance different aspects of song behavior. Copyright 2009. Published by Elsevier B.V.

  14. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Science.gov (United States)

    Wiley, Teresa S.; Haraldsen, Jason T.

    2012-03-01

    We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  15. The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

    Directory of Open Access Journals (Sweden)

    Teresa S. Wiley

    2012-03-01

    Full Text Available We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

  16. Reversal of cycloheximide-induced memory disruption by AIT-082 (Neotrofin) is modulated by, but not dependent on, adrenal hormones.

    Science.gov (United States)

    Yan, Rongzi; Nguyen, Quang; Gonzaga, James; Johnson, Mai; Ritzmann, Ronald F; Taylor, Eve M

    2003-04-01

    AIT-082 (Neotrofin), a hypoxanthine derivative, has been shown to improve memory in both animals and humans. In animals, adrenal hormones modulate the efficacy of many memory-enhancing compounds, including piracetam and tacrine (Cognex). To investigate the role of adrenal hormones in the memory-enhancing action of AIT-082. Plasma levels of adrenal hormones (corticosterone and aldosterone) in mice were significantly reduced by surgical or chemical (aminoglutethimide) adrenalectomy or significantly elevated by oral administration of corticosterone. The effects of these hormone level manipulations on the memory-enhancing activity of AIT-082 and piracetam were evaluated using a cycloheximide-induced amnesia/passive avoidance model. As previously reported by others, the memory enhancing action of piracetam was abolished by adrenalectomy. In contrast, the memory enhancement by 60 mg/kg AIT-082 (IP) was unaffected. However, a sub-threshold dose of AIT-082 (0.1 mg/kg, IP) that did not improve memory in control animals did improve memory in adrenalectomized animals. These data suggested that, similar to piracetam and tacrine, the memory enhancing action of AIT-082 might be inhibited by high levels of adrenal hormones. As expected, corticosterone (30 and 100 mg/kg) inhibited the action of piracetam, however no dose up to 100 mg/kg corticosterone inhibited the activity of AIT-082. These data suggest that while AIT-082 function is not dependent on adrenal hormones, it is modulated by them. That memory enhancement by AIT-082 was not inhibited by high plasma corticosterone levels may have positive implications for its clinical utility, given that many Alzheimer's disease patients have elevated plasma cortisol levels.

  17. Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.

    Science.gov (United States)

    Sant'Anna, Gabriela Dos Santos; Brum, Ilma Simoni; Branchini, Gisele; Pizzolato, Lolita Schneider; Capp, Edison; Corleta, Helena von Eye

    2017-08-01

    Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.

  18. Maternal hormonal interventions as a risk factor for Autism Spectrum Disorder: an epidemiological assessment from India.

    Science.gov (United States)

    Mamidala, Madhu Poornima; Polinedi, Anupama; Kumar, P T V Praveen; Rajesh, N; Vallamkonda, Omsai Ramesh; Udani, Vrajesh; Singhal, Nidhi; Rajesh, Vidya

    2013-12-01

    Globalization and women empowerment have led to stressful life among Indian women. This stress impairs women's hormonal makeup and menstrual cycle, leading to infertility. National Family Health Survey-3 (NFHS-3) reports a decline in fertility status in India, indicating a rise in various infertility treatments involving hormonal interventions. No studies are available from India on the risk association link between maternal hormonal treatments and ASD. Hence, this study explores the association of maternal hormonal interventions with risk for ASD. Parents of 942 children (471 ASD and 471 controls) across 9 cities in India participated in the questionnaire-based study. The questionnaire was pilot tested and validated for its content and reliability as a psychometric instrument. Data collection was done at 70 centres through direct interaction with parents and with the help of trained staff. Statistical analysis of data was carried out using SAS 9.1.3. Out of the 471 ASD cases analysed, 58 mothers had undergone hormonal interventions (12.3 percent) while there were only 22 mothers among controls who underwent hormonal interventions (4.6 percent). According to logistic regression analysis maternal hormonal intervention (OR=2.24) was a significant risk factor for ASD.

  19. Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

    International Nuclear Information System (INIS)

    Jaeaeskelaeinen, T.; Huhtakangas, J.; Maeenpaeae, P.H.

    2005-01-01

    The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D 3 (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH) 2 D 3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y

  20. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bitencourt, C.S. [Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I. [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-03-02

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

  1. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    International Nuclear Information System (INIS)

    Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

    2012-01-01

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

  2. The effects of social isolation on steroid hormone levels are modulated by previous social status and context in a cichlid fish.

    Science.gov (United States)

    Galhardo, L; Oliveira, R F

    2014-01-01

    Social isolation is a major stressor which impacts the physiology, behaviour and health of individuals in gregarious species. However, depending on conditional and contextual factors, such as social status and group composition, social isolation may be perceived differently by different individuals or even by the same individuals at different times. Here we tested the effects of social status (territorial vs. non-territorial) and previous group composition (i.e. type of social group: mixed sex group with two territorial males, TT vs. mixed sex group with one territorial and one non-territorial male, TnT) on the hormonal response (androgens and cortisol) to social isolation in a cichlid fish (Oreochromis mossambicus). The different steroid hormones measured responded differentially to social isolation, and their response was modulated by social factors. Social isolation elicited a decrease of 11-keto formation only in territorial males, whereas non-territorial males present a non-significant trend for increasing KT levels. Testosterone did not respond to social isolation. Cortisol only increased in isolated individuals from TnT groups irrespective of social status (i.e. both in territorials and non-territorials). These results suggest that it is the perception of social isolation and not the objective structure of the situation that triggers the hormonal response to isolation. © 2013.

  3. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    International Nuclear Information System (INIS)

    Ahren, B.

    1987-01-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse

  4. Thyroid hormone and retinoic acid nuclear receptors: specific ligand-activated transcription factors

    International Nuclear Information System (INIS)

    Brtko, J.

    1998-01-01

    Transcriptional regulation by both the thyroid hormone and the vitamin A-derived 'retinoid hormones' is a critical component in controlling many aspects of higher vertebrate development and metabolism. Their functions are mediated by nuclear receptors, which comprise a large super-family of ligand-inducible transcription factors. Both the thyroid hormone and the retinoids are involved in a complex arrangement of physiological and development responses in many tissues of higher vertebrates. The functions of 3,5,3'-triiodothyronine (T 3 ), the thyromimetically active metabolite of thyroxine as well as all-trans retinoic acid, the biologically active vitamin A metabolite are mediated by nuclear receptor proteins that are members of the steroid/thyroid/retinoid hormone receptor family. The functions of all members of the receptor super family are discussed. (authors)

  5. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  6. Crustacean hyperglycemic hormone (cHH as a modulator of aggression in crustacean decapods.

    Directory of Open Access Journals (Sweden)

    Laura Aquiloni

    Full Text Available Biogenic amines, particularly serotonin, are recognised to play an important role in controlling the aggression of invertebrates, whereas the effect of neurohormones is still underexplored. The crustacean Hyperglycemic Hormone (cHH is a multifunctional member of the eyestalk neuropeptide family. We expect that this neuropeptide influences aggression either directly, by controlling its expression, or indirectly, by mobilizing the energetic stores needed for the increased activity of an animal. Our study aims at testing such an influence and the possible reversion of hierarchies in the red swamp crayfish, Procambarus clarkii, as a model organism. Three types of pairs of similarly sized males were formed: (1 'control pairs' (CP, n = 8: both individuals were injected with a phosphate saline solution (PBS; (2 'reinforced pairs' (RP, n = 9: the alpha alone was injected with native cHH, and the beta with PBS; (3 'inverted pairs' (IP, n = 9: the opposite of (2. We found that, independently of the crayfish's prior social experience, cHH injections induced (i the expression of dominance behaviour, (ii higher glycemic levels, and (iii lower time spent motionless. In CP and RP, fight intensity decreased with the establishment of dominance. On the contrary, in IP, betas became increasingly likely to initiate and escalate fights and, consequently, increased their dominance till a temporary reversal of the hierarchy. Our results demonstrate, for the first time, that, similarly to serotonin, cHH enhances individual aggression, up to reverse, although transitorily, the hierarchical rank. New research perspectives are thus opened in our intriguing effort of understanding the role of cHH in the modulation of agonistic behaviour in crustaceans.

  7. Investigating the Interactive Effects of Sex Steroid Hormones and Brain-Derived Neurotrophic Factor during Adolescence on Hippocampal NMDA Receptor Expression

    Directory of Open Access Journals (Sweden)

    Cushla R. McCarthny

    2018-01-01

    Full Text Available Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF. This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/− on hippocampal NMDA-R expression. Wild-type and BDNF+/− mice were gonadectomised, and females received either 17β-estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT treatment. Dorsal (DHP and ventral hippocampus (VHP were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis. Significant genotype × OVX interactions were found for GluN1 and GluN2 expression within the DHP of female mice, suggesting modulation of select NMDA-R levels by female sex hormones is mediated by BDNF. Furthermore, within the DHP BDNF+/− mice show a hypersensitive response to hormone treatment on GluN2 expression which may result from upstream alterations in TrkB phosphorylation. In contrast to the DHP, the VHP showed no effects of hormone manipulation but significant effects of genotype on NMDA-R expression. Castration had no effect on NMDA-R expression; however, androgen treatment had selective effects on GluN2B. These data show case distinct, interactive roles for sex steroid hormones and BDNF in the regulation of NMDA-R expression that are dependent on dorsal versus ventral hippocampal region.

  8. The FOXO transcription factor controls insect growth and development by regulating juvenile hormone degradation in the silkworm, Bombyx mori.

    Science.gov (United States)

    Zeng, Baosheng; Huang, Yuping; Xu, Jun; Shiotsuki, Takahiro; Bai, Hua; Palli, Subba Reddy; Huang, Yongping; Tan, Anjiang

    2017-07-14

    Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO ( BmFOXO ) to elucidate its physiological functions during development of this lepidopteran insect. The BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and showed precocious metamorphosis, pupating at the end of the fourth instar (trimolter) rather than at the end of the fifth instar as in the wild-type (WT) animals. However, different from previous reports on precocious metamorphosis caused by juvenile hormone (JH) deficiency in silkworm mutants, the total developmental time of the larval period in the FOXO-M was comparable with that of the WT. Exogenous application of 20-hydroxyecdysone (20E) or of the JH analog rescued the trimolter phenotype. RNA-seq and gene expression analyses indicated that genes involved in JH degradation but not in JH biosynthesis were up-regulated in the FOXO-M compared with the WT animals. Moreover, we identified several FOXO-binding sites in the promoter of genes coding for JH-degradation enzymes. These results suggest that FOXO regulates JH degradation rather than its biosynthesis, which further modulates hormone homeostasis to control growth and development in B. mori In conclusion, we have uncovered a pivotal role for FOXO in regulating JH signaling to control insect development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Thyroid hormones modulate occurrence and termination of ventricular fibrillation by both long-term and acute actions

    Czech Academy of Sciences Publication Activity Database

    Knezl, V.; Soukup, Tomáš; Okruhlicová, L.; Slezák, J.; Tribulová, N.

    2008-01-01

    Roč. 57, Suppl.2 (2008), S91-S96 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA304/05/0327 Institutional research plan: CEZ:AV0Z50110509 Keywords : ventricular fibrillation * sinus rhythm restoration * thyroid hormone Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

  10. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    Introduction: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or ...

  11. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  12. Hormonal, lifestyle, and dietary factors in relation to leptin among elderly men.

    Science.gov (United States)

    Lagiou, P; Signorello, L B; Mantzoros, C S; Trichopoulos, D; Hsieh, C C; Trichopoulou, A

    1999-01-01

    Leptin, the adipocyte-secreted protein product of the ob gene, has been strongly linked to obesity and is believed to play a role in the regulation of the reproductive system. This study examines the potential influence of lifestyle and dietary factors, as well as of other hormones, on serum levels of leptin. The authors studied a population of 48 healthy elderly Greek men. Sera from these men were analyzed for leptin, several steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1. The authors also utilized data from food frequency questionnaires and information on demographic, anthropometric, and lifestyle (cigarette smoking, alcohol and coffee drinking) factors. Using linear regression modeling, serum leptin levels were inversely associated with testosterone and positively associated with estradiol and dehydroepiandrosterone sulfate, after adjustment for the other hormones and body mass index (BMI). Leptin levels in men with a BMI >30 kg/m2 were 170% higher than in men with a BMI coffee drinking, or total energy intake, on the other. When total energy intake was separated into its three major components (carbohydrate, fat, and protein), it appeared that fat intake may have an isocalorically differential effect on serum leptin levels; one marginal quintile increase in fat intake corresponded to an 11% increase in leptin (95% CI 0-24%). Serum levels of leptin may be influenced by other endocrine factors, especially testosterone and estradiol, and may be positively associated with excess fat intake independently of obesity.

  13. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    Science.gov (United States)

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  14. Female reproductive factors, menopausal hormone use, and Parkinson’s disease

    Science.gov (United States)

    Liu, Rui; Baird, Donna; Park, Yikyung; Freedman, Neal D.; Huang, Xuemei; Hollenbeck, Albert; Blair, Aaron; Chen, Honglei

    2014-01-01

    Objective To examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson’s disease (PD) among postmenopausal women. Methods The study comprised 119,166 postmenopausal women ages 50–71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995–1996 and a follow-up survey in 2004–2006. A total of 410 self-reported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression models. Results PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at ages 50–54 years, the ORs were 1.18, (95% CI 0.78–1.79) for women with natural menopause at ages <45, 1.19 (0.88–1.61) for ages 45–49, and 1.33 (0.91–1.93) for ages 55 or later. We found that oral contraceptive use for ≥10 years (vs. never use) was associated with lower PD risk (OR=0.59; 0.38–0.92) but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users of <5 years showed a higher risk of PD (OR=1.52; 1.11–2.08). However, no associations were observed for past hormone users or current users of ≥5 years. Conclusions Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. PMID:24352877

  15. Hormones and Antibiotics in Nature: A Laboratory Module Designed to Broaden Undergraduate Perspectives on Typically Human-Centered Topics

    Directory of Open Access Journals (Sweden)

    Carolyn F. Weber

    2014-07-01

    Full Text Available Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011 to the topics “hormones” and “antibiotics” in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1 fungi may promote fern growth via hormone production, 2 novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3 subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection, but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.

  16. Hormonal receptors and vascular endothelial growth factor in juvenile nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.

    Science.gov (United States)

    Liu, Zhuofu; Wang, Jingjing; Wang, Huan; Wang, Dehui; Hu, Li; Liu, Quan; Sun, Xicai

    2015-01-01

    This work demonstrated that juvenile nasopharyngeal angiofibromas (JNAs) express high levels of hormone receptors and vascular endothelial growth factor (VEGF) compared with normal nasal mucosa. The interaction between hormone receptors and VEGF may be involved in the initiation and growth of JNA. JNA is a rare benign tumor that occurs almost exclusively in male adolescents. Although generally regarded as a hormone-dependent tumor, this has not been proven in previous studies. The aim of this study was to investigate the role of hormone receptors in JNA and the relationship with clinical characteristics. Standard immunohistochemical microarray analysis was performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies for androgen receptor (AR), estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), progesterone receptor (PR), and VEGF were examined, and the relationships of receptor expression with age, tumor stage, and bleeding were evaluated. RESULTS showed that JNA expressed ER-α (92.9%), ER-β (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level of VEGF was linked to elevated ER-α and ER-β. There was no significant relationship between hormonal receptors and age at diagnosis, tumor stage or bleeding. However, overexpression of ER-α was found to be an indicator of poor prognosis (p = 0.031).

  17. Fibroblast growth factor 21, fibroblast growth factor receptor 1, and β-Klotho expression in bovine growth hormone transgenic and growth hormone receptor knockout mice.

    Science.gov (United States)

    Brooks, Nicole E; Hjortebjerg, Rikke; Henry, Brooke E; List, Edward O; Kopchick, John J; Berryman, Darlene E

    Although growth hormone (GH) and fibroblast growth factor 21 (FGF21) have a reported relationship, FGF21 and its receptor, fibroblast growth factor receptor 1 (FGFR1) and cofactor β-Klotho (KLB), have not been analyzed in chronic states of altered GH action. The objective of this study was to quantify circulating FGF21 and tissue specific expression of Fgf21, Fgfr1, and Klb in mice with modified GH action. Based on previous studies, we hypothesized that bovine GH transgenic (bGH) mice will be FGF21 resistant and GH receptor knockout (GHR-/-) mice will have normal FGF21 action. Seven-month-old male bGH mice (n=9) and wild type (WT) controls (n=10), and GHR-/- mice (n=8) and WT controls (n=8) were used for all measurements. Body composition was determined before dissection, and tissue weights were measured at the time of dissection. Serum FGF21 levels were evaluated by ELISA. Expression of Fgf21, Fgfr1, and Klb mRNA in white adipose tissue (AT), brown AT, and liver were evaluated by reverse transcription quantitative PCR. As expected, bGH mice had increased body weight (p=3.70E -8 ) but decreased percent fat mass (p=4.87E -4 ). Likewise, GHR-/- mice had decreased body weight (p=1.78E -10 ) but increased percent fat mass (p=1.52E -9 ), due to increased size of the subcutaneous AT depot when normalized to body weight (p=1.60E -10 ). Serum FGF21 levels were significantly elevated in bGH mice (p=0.041) and unchanged in GHR-/- mice (p=0.88). Expression of Fgf21, Fgfr1, and Klb mRNA in white AT and liver were downregulated or unchanged in both bGH and GHR-/- mice. The only exception was Fgf21 expression in brown AT of GHR-/-, which trended toward increased expression (p=0.075). In accordance with our hypothesis, we provide evidence that circulating FGF21 is increased in bGH animals, but remains unchanged in GHR-/- mice. Downregulation or no change in Fgf21, Fgfr1, and Klb expression are seen in white AT, brown AT, and liver of bGH and GHR-/- mice when compared to their

  18. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Science.gov (United States)

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  19. Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

    Science.gov (United States)

    Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

    2006-01-01

    Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

  20. Hypothalamic growth hormone releasing factor deficiency following cranial irradiation

    International Nuclear Information System (INIS)

    Ahmed, S.R.; Shalet, S.M.

    1984-01-01

    The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1-44) on GH release has been studied in 10 patients with radiation-induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/1) and to arginine stimulation (median peak GH 2.9 mU/1), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 μg) of hp GRF1-44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/1; range 22-57 mU/1) to hp GRF1-44, similar in magnitude and timing to that seen in th four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1-44, ITT and to arginine was a result of radiation-induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future. (author)

  1. Hormonal and dietary factors in acne vulgaris versus controls.

    Science.gov (United States)

    Stewart, Thomas Jonathan; Bazergy, Carl

    2018-01-01

    Background : Acne vulgaris is an inflammatory skin disorder with not as yet fully understood pathogenesis. In this controlled study, we assessed acne vulgaris patients for several possible pathogenic factors such as vitamin D deficiency, vegan diet, increased body mass index (BMI) and positive anti-transglutaminase antibody. Methods : We screened 10 years of records at a family medicine clinic for patients diagnosed with acne vulgaris. In eligible subjects, we collected data regarding 25-hydroxylvitamin D levels, BMI, dietary preference and serum IgA tissue transglutaminase levels. Controls were age- (+/- 12 months) and sex-matched patients seen during the study period without a diagnosis of acne vulgaris. Results : 453 patients were given a diagnosis of acne vulgaris during the study period. Compared with controls, we found significant associations between vitamin D deficiency (4.0U/mL) and a diagnosis of acne vulgaris. Conclusions : Our study adds important information to the current body of literature in pursuit of elucidating the pathogenesis of this complex multifactorial disease.

  2. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development

    International Nuclear Information System (INIS)

    Veldhoen, Nik; Skirrow, Rachel C.; Osachoff, Heather; Wigmore, Heidi; Clapson, David J.; Gunderson, Mark P.; Van Aggelen, Graham; Helbing, Caren C.

    2006-01-01

    We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) α and β, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10 -11 mol/g body weight 3,5,3'-triiodothyronine (T 3 ) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10 nM T 3 . Tadpoles pretreated with triclosan concentrations as low as 0.15 ± 0.03 μg/L for 4 days showed increased hindlimb development and a decrease in total body weight following T 3 administration. Triclosan exposure also resulted in decreased T 3 -mediated TRβ mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T 3 treatment whereas TRα and BTEB were unaffected. Triclosan alone altered thyroid hormone receptor α transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T 3 plus nominal concentrations of triclosan as low as 0.03 μg/L for 24 h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development

  3. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development

    Energy Technology Data Exchange (ETDEWEB)

    Veldhoen, Nik [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Skirrow, Rachel C. [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Osachoff, Heather [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Wigmore, Heidi [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Clapson, David J. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Gunderson, Mark P. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Van Aggelen, Graham [Pacific Environmental Science Centre, 2645 Dollarton Highway, North Vancouver, British Columbia V7H 1V2 (Canada); Helbing, Caren C. [Department of Biochemistry and Microbiology, P.O. Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada)]. E-mail: chelbing@uvic.ca

    2006-12-01

    We investigated whether exposure to environmentally relevant concentrations of the bactericidal agent, triclosan, induces changes in the thyroid hormone-mediated process of metamorphosis of the North American bullfrog, Rana catesbeiana and alters the expression profile of thyroid hormone receptor (TR) {alpha} and {beta}, basic transcription element binding protein (BTEB) and proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic tadpoles were immersed in environmentally relevant concentrations of triclosan and injected with 1 x 10{sup -11} mol/g body weight 3,5,3'-triiodothyronine (T{sub 3}) or vehicle control. Morphometric measurements and steady-state mRNA levels obtained by quantitative polymerase chain reaction were determined. mRNA abundance was also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10 nM T{sub 3}. Tadpoles pretreated with triclosan concentrations as low as 0.15 {+-} 0.03 {mu}g/L for 4 days showed increased hindlimb development and a decrease in total body weight following T{sub 3} administration. Triclosan exposure also resulted in decreased T{sub 3}-mediated TR{beta} mRNA expression in the tadpole tail fin and increased levels of PCNA transcript in the brain within 48 h of T{sub 3} treatment whereas TR{alpha} and BTEB were unaffected. Triclosan alone altered thyroid hormone receptor {alpha} transcript levels in the brain of premetamorphic tadpoles and induced a transient weight loss. In XTC-2 cells, exposure to T{sub 3} plus nominal concentrations of triclosan as low as 0.03 {mu}g/L for 24 h resulted in altered thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan disrupts thyroid hormone-associated gene expression and can alter the rate of thyroid hormone-mediated postembryonic anuran development.

  4. Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

    Directory of Open Access Journals (Sweden)

    Parvinder Kaur

    2011-01-01

    Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

  5. Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

    Science.gov (United States)

    Wei, Junxiang; Gerlich, Jessica; Genuneit, Jon; Nowak, Dennis; Vogelberg, Christian; von Mutius, Erika; Radon, Katja

    2015-07-01

    Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Steroid Hormone (20-Hydroxyecdysone) Modulates the Acquisition of Aversive Olfactory Memories in Pollen Forager Honeybees

    Science.gov (United States)

    Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.

    2013-01-01

    Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…

  7. Hormones and the Autonomic Nervous System are Involved in Suprachiasmatic Nucleus Modulation of Glucose Homeostasis

    NARCIS (Netherlands)

    Ruiter, M.; Buijs, R.M.; Kalsbeek, A.

    2006-01-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore,

  8. Hormones and the autonomic nervous system are involved in suprachiasmatic nucleus modulation of glucose homeostasis

    NARCIS (Netherlands)

    Ruiter, Marieke; Buijs, Ruud M.; Kalsbeek, Andries

    2006-01-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore,

  9. Hormonal fluctuations during the estrous cycle modulate Heme Oxygenase-1 expression in the uterus

    Directory of Open Access Journals (Sweden)

    Maria Laura Zenclussen

    2014-03-01

    Full Text Available Deletion of the Heme Oxygenase-1 (Hmox1 locus in mice results in intrauterine lethality. The expression of the heme catabolyzing enzyme encoded by this gene, namely HO 1, is required to successfully support reproductive events. We have previously observed that HO-1 acts at several key events in reproduction ensuring pregnancy. HO-1 defines ovulation, positively influences implantation and placentation and ensures fetal growth and survival. Here, we embarked on a study aimed to determine whether hormonal changes during the estrous cycle in the mouse define HO-1 expression, thus influencing receptivity. We analyzed the serum levels of progesterone and estrogen by ELISA and HO-1 mRNA expression in uterus by real time RT-PCR at the metestrus, proestrus, estrus and diestrus phases of the estrous cycle. Further, we studied the HO-1 protein expression by Western Blot upon hormone addition to cultured uterine AN3 cells. We observed that HO-1 variations in uterine tissue correlated to changes in hormonal levels at different phases of the estrus cycle. In vitro, HO-1 protein levels in AN3 cells augmented after the addition of physiological concentrations of progesterone and estradiol, which confirmed our in vivo observations. Our data suggest an important role for hormones in HO-1 regulation in uterus that has a significant impact in receptivity and later on blastocyst implantation.

  10. Modulation of DNA binding by gene-specific transcription factors.

    Science.gov (United States)

    Schleif, Robert F

    2013-10-01

    The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

  11. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  12. Hormones and growth factors in the pathogenesis of spinal ligament ossification.

    Science.gov (United States)

    Li, Hai; Jiang, Lei-Sheng; Dai, Li-Yang

    2007-08-01

    Ossification of the spinal ligaments (OSL) is a pathologic condition that causes ectopic bone formation and subsequently results in various degrees of neurological deficit, but the etiology of OSL remains almost unknown. Some systemic hormones, such as 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), insulin and leptin, and local growth factors, such as transforming growth factor-beta (TGF-beta), and bone morphogenetic protein (BMP), have been studied and are thought to be involved in the initiation and development of OSL. This review article summarizes these studies, delineates the possible mechanisms, and puts forward doubts and new questions. The related findings from studies of genes and target cells in the ligament of OSL are also discussed. Although these findings may be helpful in understanding the pathogenesis of OSL, much more research needs to be conducted in order to investigate the nature of OSL.

  13. Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications.

    Science.gov (United States)

    Pasqualini, Jorge R; Chetrite, Gérard S

    2012-04-01

    The bioformation and transformation of estrogens and other hormones in the breast tissue as a result of the activity of the various enzymes involved attract particular attention for the role they play in the development and pathogenesis of hormone-dependent breast cancer. The enzymatic process concerns the aromatase, which transforms androgens into estrogens; the sulfatase, which hydrolyzes the biologically inactive sulfates to the active hormone; the 17β-hydroxysteroid dehydrogenases, which are involved in the interconversion estradiol/estrone or testosterone/androstenedione; hydroxylases, which transform estrogens into mitotic and antimitotic derivatives; and sulfotransferases and glucuronidases, which, respectively convert into the biologically inactive sulfates and glucuronides. These enzymatic activities are more intense in the carcinoma than in the normal tissue. Concerning aromatase, the application of antiaromatase agents has been largely developed in the treatment of breast cancer patients, with very positive results. Various studies have shown that the activity levels of these enzymes and their mRNA can be involved as interesting prognostic factors for breast cancer. In conclusion, the application of new antienzymatic molecules can open attractive perspectives in the treatment of hormone-dependent breast cancer.

  14. A case-control study of hormonal exposures as etiologic factors for ALS in women : Euro-MOTOR

    NARCIS (Netherlands)

    Rooney, James P K; Visser, Anne E; D'Ovidio, Fabrizio; Vermeulen, Roel; Beghi, Ettore; Chio, Adriano; Veldink, Jan H.; Logroscino, Giancarlo; van den Berg, Leonard H.; Hardiman, Orla

    2017-01-01

    OBJECTIVE: To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. METHODS: ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history,

  15. Sex differences in the activity of mice: modulation by postnatal gonadal hormones.

    Science.gov (United States)

    Broida, J; Svare, B

    1984-03-01

    A series of six experiments was performed to examine the influence of postnatal-gonadal-hormone exposure on home-cage activity in Rockland-Swiss albino mice. Intact females were more active than their male counterparts and gonadectomy in adulthood, while reducing levels of the behavior in both sexes, did not eliminate the gender difference. Males that were castrated on the day of birth were more active than animals castrated 5, 10, or 25 days later. Also, females treated with testosterone propionate on the day of birth were less active than oil-treated controls and females exposed to the steroid 10 days after birth. Thus, perinatal exposure to gonadal hormones suppresses adult levels of home-cage activity in mice.

  16. [FEMALE STEROID HORMONES - MODULATORS OF IMMUNE RESPONSE TO GENITAL CHLAMYDIA TRACHOMATIS INFECTION.

    Science.gov (United States)

    Kovachev, E; Ivanov, S; Bechev, B; Angelova, M; Grueva, E; Kolev, N; Ivanova, V

    In the recent years according to WHO, genital chlamydia is the mos't common sexually transmitted infection. Chlamydia Trachomatis is an intracellular parasite which target are the tubular epithelial cells of the urethra, endocervix, endometrium, endosalpinx, conjunctiva, synovial lining of the joints, Glisson's capsule of the liver Our study, as well as some international researches, shows that in the cases of genital chlamydia there are changes in the ovarian hormones (estradiol and progesterone), their impact on the immune system and their importance for the development and the complications of the infection with Chlamydia trachomatis. The physiological level of the steroid hormones in its turn contributes for the normalization of the local immunity and reduces the possibility of recurrences.

  17. DNA methylation affects the lifespan of honey bee (Apis mellifera L.) workers - Evidence for a regulatory module that involves vitellogenin expression but is independent of juvenile hormone function.

    Science.gov (United States)

    Cardoso-Júnior, Carlos A M; Guidugli-Lazzarini, Karina R; Hartfelder, Klaus

    2018-01-01

    The canonic regulatory module for lifespan of honey bee (Apis mellifera) workers involves a mutual repressor relationship between juvenile hormone (JH) and vitellogenin (Vg). Compared to vertebrates, however, little is known about a possible role of epigenetic factors. The full genomic repertoire of DNA methyltransferases (DNMTs) makes the honey bee an attractive emergent model for studying the role of epigenetics in the aging process of invertebrates, and especially so in social insects. We first quantified the transcript levels of the four DNMTs encoding genes in the head thorax and abdomens of workers of different age, showing that dnmt1a and dnmt3 expression is up-regulated in abdomens of old workers, whereas dnmt1b and dnmt2 are down-regulated in heads of old workers. Pharmacological genome demethylation by RG108 treatment caused an increase in worker lifespan. Next, we showed that the genomic DNA methylation status indirectly affects vitellogenin gene expression both in vitro and in vivo in young workers, and that this occurs independent of caloric restriction or JH levels, suggesting that a non-canonical circuitry may be acting in parallel with the JH/Vg module to regulate the adult life cycle of honey bee workers. Our data provide evidence that epigenetic factors play a role in regulatory networks associated with complex life history traits of a social insect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo.

    Science.gov (United States)

    Tucker, D C; Torres, A

    1992-02-01

    To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.

  19. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

    Directory of Open Access Journals (Sweden)

    Mayte Alvarez-Crespo

    2016-04-01

    Full Text Available Objective: Classically, metabolic effects of thyroid hormones (THs have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3 could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1 KO mice. Methods: Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results: We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK and elevated body temperature (0.7 °C. UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY and agouti-related peptide (AgRP and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning” of inguinal white adipose tissue (iWAT. Conclusions: We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. Keywords: AMPK, Brown adipose tissue, Hypothalamus, Thyroid hormones, UCP1

  20. Dietary TiO2 particles modulate expression of hormone-related genes in Bombyx mori.

    Science.gov (United States)

    Shi, Guofang; Zhan, Pengfei; Jin, Weiming; Fei, JianMing; Zhao, Lihua

    2017-08-01

    Silkworm (Bombyx mori) is an economically beneficial insect. Its growth and development are regulated by endogenous hormones. In the present study, we found that feeding titanium dioxide nanoparticles (TiO 2 NP) caused a significant increase of body size. TiO 2 NP stimulated the transcription of several genes, including the insulin-related hormone bombyxin, PI3K/Akt/TOR (where PI3K is phosphatidylinositol 3-kinase and TOR is target of rapamycin), and the adenosine 5'-monophosphateactivated protein kinase (AMPK)/target of rapamycin (TOR) pathways. Differentially expressed gene (DEG) analysis documented 26 developmental hormone signaling related genes that were differentially expressed following dietary TiO 2 NP treatment. qPCR analysis confirmed the upregulation of insulin/ecdysteroid signaling genes, such as bombyxin B-1, bombyxin B-4, bombyxin B-7, MAPK, P70S6K, PI3k, eIF4E, E75, ecdysteroid receptor (EcR), and insulin-related peptide binding protein precursor 2 (IBP2). We infer from the upregulated expression of bombyxins and the signaling network that they act in bombyxin-stimulated ecdysteroidogenesis. © 2017 Wiley Periodicals, Inc.

  1. Endurance exercise modulates levodopa induced growth hormone release in patients with Parkinson's disease.

    Science.gov (United States)

    Müller, Thomas; Welnic, Jacub; Woitalla, Dirk; Muhlack, Siegfried

    2007-07-11

    Acute levodopa (LD) application and exercise release human growth hormone (GH). An earlier trial showed, that combined stimulus of exercise and LD administration is the best provocative test for GH response in healthy participants. Objective was to show this combined effect of LD application and exercise on GH response and to investigate the impact on LD metabolism in 20 previously treated patients with Parkinson's disease (PD). We measured GH- and LD plasma concentrations following soluble 200 mg LD/50 mg benserazide administration during endurance exercise and rest on two separate consecutive days. GH concentrations significantly increased on both days, but GH release was significantly delayed during rest. LD metabolism was not altered due to exercise in a clinical relevant manner. Exercise induced a significant faster LD stimulated GH release in comparison with the rest condition. We did not find the supposed increase of LD induced GH release by endurance exercise. We assume, that only a limited amount of GH is available for GH release in the anterior pituitary following an acute 200 mg LD administration. GH disposal also depends on growth hormone releasing hormone (GHRH), which is secreted into hypothalamic portal capillaries. During the exercise condition, the resulting higher blood pressure supports blood flow and thus GHRH transport towards the GH producing cells in the pituitary. This might additionally have caused the significant faster GH release during exercise.

  2. Environmental and hormonal factors controlling reversible colour change in crab spiders.

    Science.gov (United States)

    Llandres, Ana L; Figon, Florent; Christidès, Jean-Philippe; Mandon, Nicole; Casas, Jérôme

    2013-10-15

    Habitat heterogeneity that occurs within an individual's lifetime may favour the evolution of reversible plasticity. Colour reversibility has many different functions in animals, such as thermoregulation, crypsis through background matching and social interactions. However, the mechanisms underlying reversible colour changes are yet to be thoroughly investigated. This study aims to determine the environmental and hormonal factors underlying morphological colour changes in Thomisus onustus crab spiders and the biochemical metabolites produced during these changes. We quantified the dynamics of colour changes over time: spiders were kept in yellow and white containers under natural light conditions and their colour was measured over 15 days using a spectrophotometer. We also characterised the chemical metabolites of spiders changing to a yellow colour using HPLC. Hormonal control of colour change was investigated by injecting 20-hydroxyecdysone (20E) into spiders. We found that background colouration was a major environmental factor responsible for colour change in crab spiders: individuals presented with white and yellow backgrounds changed to white and yellow colours, respectively. An ommochrome precursor, 3-OH-kynurenine, was the main pigment responsible for yellow colour. Spiders injected with 20E displayed a similar rate of change towards yellow colouration as spiders kept in yellow containers and exposed to natural sunlight. This study demonstrates novel hormonal manipulations that are capable of inducing reversible colour change.

  3. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

    Science.gov (United States)

    Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

    2009-12-01

    The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

  4. Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

    Directory of Open Access Journals (Sweden)

    Symonds Ian

    2011-06-01

    Full Text Available Abstract Background Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment. Results Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold. Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV, which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response. Conclusion Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

  5. THYROID HORMONE TREATED ASTROCYTES INDUCE MATURATION OF CEREBRAL CORTICAL NEURONS THROUGH MODULATION OF PROTEOGLYCAN LEVELS

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    Romulo Sperduto Dezonne

    2013-08-01

    Full Text Available Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within these signals, thyroid hormones (T3 and T4 play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. The lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. In this work, we investigated the effect of 3, 5, 3’-triiodothyronine-treated (T3-treated astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. In addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1 (GPC-1 and Syndecans 3 e 4 (SDC-3 e SDC-4, followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation and neuronal circuitry recover.

  6. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

    Science.gov (United States)

    Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

    2016-01-01

    Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

  7. Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.

    Science.gov (United States)

    Nelson, Anita L

    2015-01-01

    As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma. This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs. Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.

  8. Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

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    Marvin Paulo Lins

    Full Text Available BACKGROUND: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC in the presence of laminin. RESULTS: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4-CD8- and single-positive CD4+ and CD8+ thymocytes. A decrease in cell number was noted in double-positive (CD4+CD8+ thymocytes. CONCLUSIONS: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

  9. Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in pre-menopausal women

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    Sarah M Bernhardt

    2016-11-01

    Full Text Available Clinics are increasingly adopting gene expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumour. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from post-menopausal women. Thus, the accuracy of such tests has not been explored in the context of the hormonal fluctuations in estrogen and progesterone that occur during the menstrual cycle in pre-menopausal women. Concordance between traditional methods of subtyping and the new tests in pre-menopausal women is likely to depend on the stage of the menstrual cycle at which the tissue sample is taken, and the relative effect of hormones on expression of genes versus proteins. The lack of knowledge around the effect of fluctuating estrogen and progesterone on gene expression in breast cancer patients raises serious concerns for intrinsic subtyping in pre-menopausal women, which comprise about 25% of breast cancer diagnoses. Further research on the impact of the menstrual cycle on intrinsic breast cancer profiling is required if pre-menopausal women are to benefit from the new technology of intrinsic subtyping.

  10. Hormones and the autonomic nervous system are involved in suprachiasmatic nucleus modulation of glucose homeostasis.

    Science.gov (United States)

    Ruiter, Marieke; Buijs, Ruud M; Kalsbeek, Andries

    2006-05-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore, changes in energy expenditure associated with the light-dark cycle induce variations in the plasma glucose concentration that are more gradual. Organisms take advantage of adapting their internal physiology to the predictable daily changes in energy expenditure, because it enables them to anticipate these changes and to prevent unnecessary disturbance of homeostasis. The hypothalamic biological clock, located in the suprachiasmatic nucleus (SCN), receives light information from the eyes and transmits this information to the rest of the body to synchronize physiology to the environment. Here we review several studies providing evidence for biological clock control of the daily variation in several aspects of glucose metabolism. Although both hormones and the autonomic nervous system can stimulate glucose uptake or production by organs in the periphery, we have shown that the biological clock control of glucose metabolism mostly occurs through the autonomic nervous system. The critical involvement of the biological clock is also indicated by several studies, indicating that disturbance of the biological clock is often associated with metabolic diseases, such as obesity, diabetes mellitus and hypertension.

  11. Learning with three factors: modulating Hebbian plasticity with errors.

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    Kuśmierz, Łukasz; Isomura, Takuya; Toyoizumi, Taro

    2017-10-01

    Synaptic plasticity is a central theme in neuroscience. A framework of three-factor learning rules provides a powerful abstraction, helping to navigate through the abundance of models of synaptic plasticity. It is well-known that the dopamine modulation of learning is related to reward, but theoretical models predict other functional roles of the modulatory third factor; it may encode errors for supervised learning, summary statistics of the population activity for unsupervised learning or attentional feedback. Specialized structures may be needed in order to generate and propagate third factors in the neural network. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Serum Growth Hormone and Insulin-Like Growth Factor-1 Levels in Women with Postadolescent Acne

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    Mualla Polat

    2010-06-01

    Full Text Available Background and Design: Acne vulgaris is an inflammatory disease of pilosebaceous unit. It usually starts after puberty but may continue into adulthood. We studied Growth hormone (GH and insulin-like growth factor (IGF-1 levels in women patients with acne vulgaris in whom all other hormon levels were normal. We aimed to show any relation of the acne vulgaris lesion type and GH and IGF-1 levels. Material and Method: The study conducted on the postadolesance period woman patients applying to out patient dermatology department with complaint of acne symptoms between Semtember 2005 and July 2006. All other hormonal parameters were normal in patients. 25 healthy similar age women were accepted as control. IGF-I and GH were quantified by solid-phase competitive chemiluminescence assays. Results: There was no difference according to age between the groups (p=0.726. The mean IGF-1 level was 336.5±112.88 ng/ml in patients and 194±31.32 ng/ml in control; the difference was significantly important (p=0.000. The mean GH level was 3.16±4.35 µIU/ml in patients and 1.15±1.21 µIU/ml in control; and the diffrence was not found as important (p=0.03. IGF-1 level was significantly important in patients with noduler involvement (p=0.015, and GH level was also significantly important in patients with cystic involvement (p=0.05. Conclusion: We supported the hypothesis that GH and IGF-1 levels were important in postadolasence period women patients with acne vulgaris. We recommend new studies comparing GH and IGF-1 levels in adolesence and postadolesence period women patients in order to support the role of these hormones in pathogenesis of acne vulgaris.

  13. The transcription factor Krüppel homolog 1 is linked to hormone mediated social organization in bees

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    Fan Yongliang

    2010-04-01

    Full Text Available Abstract Background Regulation of worker behavior by dominant queens or workers is a hallmark of insect societies, but the underlying molecular mechanisms and their evolutionary conservation are not well understood. Honey bee and bumble bee colonies consist of a single reproductive queen and facultatively sterile workers. The queens' influences on the workers are mediated largely via inhibition of juvenile hormone titers, which affect division of labor in honey bees and worker reproduction in bumble bees. Studies in honey bees identified a transcription factor, Krüppel-homolog 1 (Kr-h1, whose expression in worker brains is significantly downregulated in the presence of a queen or queen pheromone and higher in forager bees, making this gene an ideal candidate for examining the evolutionary conservation of socially regulated pathways in Hymenoptera. Results In contrast to honey bees, bumble bees foragers do not have higher Kr-h1 levels relative to nurses: in one of three colonies levels were similar in nurses and foragers, and in two colonies levels were higher in nurses. Similarly to honey bees, brain Kr-h1 levels were significantly downregulated in the presence versus absence of a queen. Furthermore, in small queenless groups, Kr-h1 levels were downregulated in subordinate workers with undeveloped ovaries relative to dominant individuals with active ovaries. Brain Kr-h1 levels were upregulated by juvenile hormone treatment relative to a vehicle control. Finally, phylogenetic analysis indicates that KR-H1 orthologs are presence across insect orders. Though this protein is highly conserved between honey bees and bumble bees, there are significant differences between orthologs of insects from different orders. Conclusions Our results suggest that Kr-h1 is associated with juvenile hormone mediated regulation of reproduction in bumble bees. The expression of this transcription factor is inhibited by the queen and associated with endocrine mediated

  14. Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice.

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    Sadagurski, Marianna; Landeryou, Taylor; Cady, Gillian; Kopchick, John J; List, Edward O; Berryman, Darlene E; Bartke, Andrzej; Miller, Richard A

    2015-12-01

    Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived. Median longevity is also increased in mice with deletion of hypothalamic GH-releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6-week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR(-/-) mice lead to reduced formation of both orexigenic agouti-related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18-month-old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF-1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF-1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early-life disruption of GH signaling produces long-term hypothalamic changes that may contribute to the longevity of GH-deficient and GH-resistant mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  15. Prognostic Factors for Hormone Sensitive Metastatic Prostate Cancer: Impact of Disease Volume

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    Alhanafy, Alshimaa Mahmoud; Zanaty, Fouad; Ibrahem, Reda; Omar, Suzan

    2018-04-27

    Background and Aim: The optimal management of metastatic hormone-sensitive prostate cancer has been controversial in recent years with introduction of upfront chemohormonal treatment based on results of several Western studies. This changing landscape has renewed interest in the concept “disease volume”, the focus of the present study is the Egyptian patients. Methods: Patients with hormone sensitive metastatic prostate cancer presenting at Menoufia University Hospital, Egypt, during the period from June 2013 to May 2016, were enrolled. All received hormonal treatment. Radiologic images were evaluated and patients were stratified according to their disease volume into high or low, other clinical and pathological data that could affect survival also being collected and analyzed. Results: A total of 128 patients were included, with a median age of 70 years (53.9% ≥70). About 46% had co-morbidities, 62% having high volume disease. During the median follow up period of 28 months about half of the patients progressed and one third received chemotherapy. On univariate analysis, disease volume, performance status (PS), prostate specific antigen level (PSA) and presence of pain at presentation were identified as factors influencing overall survival. Multivariate analysis revealed the independent predictor factors for survival to be PS, PSA and disease volume. The median overall survival with 27 months was high volume versus 49 with low volume disease (hazard ratio 2.1; 95% CI 1.2 - 4.4; P=0.02). Median progression free survival was 19 months in the high volume, as compared with 48 months in the low volume disease patients (hazard ratio, 2.44; 95% CI, 1.42 – 7.4; P=0.009). Conclusions: Disease volume is a reliable predictor of survival which should be incorporated with other important factors as; patient performance status and comorbidities in treatment decision-making. Creative Commons Attribution License

  16. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

    Science.gov (United States)

    Watts, Eleanor L; Appleby, Paul N; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A; Holly, Jeff M P; Hoover, Robert N; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S; Ziegler, Regina G; Allen, Naomi E; Key, Timothy J; Travis, Ruth C

    2017-01-01

    Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a

  17. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

    Directory of Open Access Journals (Sweden)

    Eleanor L Watts

    Full Text Available Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.Circulating sex hormones in men are strongly associated with age and body mass

  18. Effect of modulated ultrahigh frequency field on behavior and hormone level in female rats under emotional stress

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    Rasulov, M.M.

    The effect of a modulated electromagnetic field (MEMF) (field frequency of 40 MHz and modulated frequency of 50 Hz, 1 h exposure daily for 30 days) on behavior and level of sexual hormones, determined from the length of the estrous cycle and of its separate phases, was studied in female Wistar rats subjected to sexual deprivation. The ratio of frequency of running to number of vertical positions (R:V) was used as an index. Activity of rats declined during the 1-h exposure to MEMF; this may indicate the direct effect of MEMF on the central nervous system. Analysis of behavior after MEMF treatments ceased showed that the R:V ratio increased from 3.2:1 to 3:1 in month 3 and reached 2:1 in month 5. The relative significance of sexual behavior (lordosis, licking of perineum) more than double in comparison with the initial level. The findings support the existence of individual differences in sensitivity to a UHF field. The data on the estrous cycle indicate the tranquilizing effect of a UHF field on the neuroendocrine system and the greater resistance of individual animals exposed to MEMF to the development of sexual neurosis. 12 references, 2 figures.

  19. Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

    Science.gov (United States)

    Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

    2016-01-01

    Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients.

  20. Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

    OpenAIRE

    Souza, Patrícia Reis de; Sales-Campos, Helioswilton; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda; Alves, Vanessa Beatriz Freitas; Chica, Javier Emílio Lazo; Nomizo, Auro; Cardoso, Cristina Ribeiro de Barros

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score...

  1. Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

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    Bahrami, A; Behzadi, Sh; Miraei-Ashtiani, S R; Roh, S-G; Katoh, K

    2013-09-15

    The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Tuning the Fano factor of graphene via Fermi velocity modulation

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    Lima, Jonas R. F.; Barbosa, Anderson L. R.; Bezerra, C. G.; Pereira, Luiz Felipe C.

    2018-03-01

    In this work we investigate the influence of a Fermi velocity modulation on the Fano factor of periodic and quasi-periodic graphene superlattices. We consider the continuum model and use the transfer matrix method to solve the Dirac-like equation for graphene where the electrostatic potential, energy gap and Fermi velocity are piecewise constant functions of the position x. We found that in the presence of an energy gap, it is possible to tune the energy of the Fano factor peak and consequently the location of the Dirac point, by a modulation in the Fermi velocity. Hence, the peak of the Fano factor can be used experimentally to identify the Dirac point. We show that for higher values of the Fermi velocity the Fano factor goes below 1/3 at the Dirac point. Furthermore, we show that in periodic superlattices the location of Fano factor peaks is symmetric when the Fermi velocity vA and vB is exchanged, however by introducing quasi-periodicity the symmetry is lost. The Fano factor usually holds a universal value for a specific transport regime, which reveals that the possibility of controlling it in graphene is a notable result.

  3. Factors associated with sex hormones and erectile dysfunction in male Taiwanese participants with obesity.

    Science.gov (United States)

    Shi, Ming-Der; Chao, Jian-Kang; Ma, Mi-Chia; Hao, Lyh-Jyh; Chao, I-Chen

    2014-01-01

    Obesity has been receiving an increasing amount of attention recently, but investigations regarding the potential impact of obesity, sexual behaviors, and sex hormones on erectile dysfunction (ED) in men have not completely clarified the association. To identify the relationship between ED, sexual behavior, sexual satisfaction, sex hormones, and obesity in older adult males in Taiwan. Data were obtained from a baseline survey of 476 older adult males (≧40 years old). Their demographic data, body mass index (BMI), sex hormones, sexual desire, sexual satisfaction, and ED status were assessed. The International Index of Erectile Function-5 (IIEF-5), Sexual Desire Inventory (SDI), and Sexual Satisfaction Scale (SSS) were used to assess ED, sexual desire, and sexual satisfaction. In all, 476 men were available for analysis. The mean age of the sample was 51.34 ± 7.84 years (range 40 to 70 years). The IIEF total score had a mean of 19.44 ± 4.98; 264 (55.5%) subjects had ED, 250 (52.9%) were currently obese (BMI ≧27), and 297 (62.4%) had metabolic syndrome. The results showed an increased risk of ED among obese men and subjects with lower levels of sex hormones and lower sexual desire. Testosterone levels were lower in subjects with obesity (P < 0.001). Among the predictors of ED, obesity (odds ratio [OR] = 1.62, 95% CI = 1.07-2.44, P = 0.021), abnormal high sensitivity C-reactive protein (hs-CRP) (OR = 10.59, 95% CI = 4.70-23.87, P < 0.001), and lower serum full testosterone (OR = 3.27, 95% CI = 2.16-4.93, P < 0.001) were significantly independent factors. This study supports the idea of a close relationship between low levels of sex hormones, sexual desire, sexual satisfaction, obesity, and ED, and also shows that low free testosterone and hs-CRP may predict ED, even in obese populations. © 2013 International Society for Sexual Medicine.

  4. Do hormone-modulating chemicals impact on reproduction and development of wild amphibians?

    Science.gov (United States)

    Orton, Frances; Tyler, Charles R

    2015-11-01

    Globally, amphibians are undergoing a precipitous decline. At the last estimate in 2004, 32% of the approximately 6000 species were threatened with extinction and 43% were experiencing significant declines. These declines have been linked with a wide range of environmental pressures from habitat loss to climate change, disease and pollution. This review evaluates the evidence that endocrine-disrupting contaminants (EDCs) - pollutants that affect hormone systems - are impacting on wild amphibians and contributing to population declines. The review is limited to anurans (frogs and toads) as data for effects of EDCs on wild urodeles (salamanders, newts) or caecilians (limbless amphibians) are extremely limited. Evidence from laboratory studies has shown that a wide range of chemicals have the ability to alter hormone systems and affect reproductive development and function in anurans, but for the most part only at concentrations exceeding those normally found in natural environments. Exceptions can be found for exposures to the herbicide atrazine and polychlorinated biphenyls in leopard frogs (Rana pipiens) and perchlorate in African clawed frogs (Xenopus laevis). These contaminants induce feminising effects on the male gonads (including 'intersex' - oocytes within testes) at concentrations measured in some aquatic environments. The most extensive data for effects of an EDC in wild amphibian populations are for feminising effects of atrazine on male gonad development in regions across the USA. Even where strong evidence has been provided for feminising effects of EDCs, however, the possible impact of these effects on fertility and breeding outcome has not been established, making inference for effects on populations difficult. Laboratory studies have shown that various chemicals, including perchlorate, polychlorinated biphenyls and bromodiphenylethers, also act as endocrine disrupters through interfering with thyroid-dependent processes that are fundamental for

  5. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

    Science.gov (United States)

    Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

    2017-12-12

    Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

  6. Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

    Directory of Open Access Journals (Sweden)

    Ricardo Borges Machado

    2010-01-01

    Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

  7. Gonadotropin-Releasing Hormone Modulates Vomeronasal Neuron Response to Male Salamander Pheromone

    Directory of Open Access Journals (Sweden)

    Celeste R. Wirsig-Wiechmann

    2012-01-01

    Full Text Available Electrophysiological studies have shown that gonadotropin-releasing hormone (GnRH modifies chemosensory neurons responses to odors. We have previously demonstrated that male Plethodon shermani pheromone stimulates vomeronasal neurons in the female conspecific. In the present study we used agmatine uptake as a relative measure of the effects of GnRH on this pheromone-induced neural activation of vomeronasal neurons. Whole male pheromone extract containing 3 millimolar agmatine with or without 10 micromolar GnRH was applied to the nasolabial groove of female salamanders for 45 minutes. Immunocytochemical procedures were conducted to visualize and quantify relative agmatine uptake as measured by labeling density of activated vomeronasal neurons. The relative number of labeled neurons did not differ between the two groups: pheromone alone or pheromone-GnRH. However, vomeronasal neurons exposed to pheromone-GnRH collectively demonstrated higher labeling intensity, as a percentage above background (75% as compared with neurons exposed to pheromone alone (63%, P < 0.018. Since the labeling intensity of agmatine within neurons signifies the relative activity levels of the neurons, these results suggest that GnRH increases the response of female vomeronasal neurons to male pheromone.

  8. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    International Nuclear Information System (INIS)

    Gracia, Tannia; Hilscherova, Klara; Jones, Paul D.; Newsted, John L.; Higley, Eric B.; Zhang, Xiaowei; Hecker, Markus; Murphy, Margaret B.; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S.; Giesy, John P.

    2007-01-01

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different

  9. Hormonal and reproductive risk factors associated with breast cancer in Isfahan patients

    Science.gov (United States)

    Tazhibi, Mehdi; Dehghani, Mohsen; Babazadeh, Shadi; Makkarian, Fariborz; Tabatabaeian, Maryam; Sadeghi, Masoumeh; Rezaei, Parisa; Faghihi, Mehri

    2014-01-01

    Background: Breast cancer is the most prevalent type of cancer among Iranian females; it is noteworthy that the condition of this type of cancer among Iranian women does not significantly differ from what has been reported from other countries. Considering the importance of this issue, identification of the backgrounds factors and risk factors of the breast cancer risk are highly needed. Therefore, the present study is aimed to compare the risk factors of resident patients of Isfahan province, Iran, with accredited risk factors by other countries and also identify the importance of each factor in the incidence of cancer. Materials and Methods: The present work is a case-control study, which was conducted in 2011. In order to conduct the study, 216 women who had been clinically identified with breast cancer were selected from Seiedo-Shohada Hospital, Isfahan, Iran, as the case group. Moreover, 41 healthy women who were the relatives of the selected patients (i.e., sisters and aunts) were selected as the control group. The data and information of the patients from 1999 to 2010 were collected from either assessing the database system of the center for breast cancer research or interviewing the patients through phone. To analyze the data, multiple logistic regression method was applied. Results: The range of age among selected individuals in this study was from 20-75 years old. The determinant factors for odds of breast cancer included in the applied multiple logistic regression model were the use of oral contraceptive pills (OCPs) (odds ratio [OR] =0.18, 95% confidence interval [CI] = 0.04-0.75) as the protective factor, hormone replacement therapy (OR = 10.2, 95% CI = 1.18-88.89) and menopause at old age (OR = 1.26, 95% CI = 1.11-2.12) as the risk factors. Furthermore, there was not seen any significant relationship between age, vocation, and marital status with odds of breast cancer in multiple model. Conclusion: Based on the results, use of OCPs as protective

  10. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  11. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  12. Steroid hormones modulate galectin-1 in the trophoblast HTR-8/SVneocell line

    Directory of Open Access Journals (Sweden)

    Bojić-Trbojević Žanka

    2008-01-01

    Full Text Available The effects of steroids on galectin-1 (gal-1 were studied in HTR-8/SVneo cells by immunocytochemistry, cell-based ELISA, the MTT proliferation test and the Matrigel TM invasion test. Dexamethasone (DEX, progesterone (PRG, and mifepristone (RU486 were used. Gal-1 was modulated in a steroid- and dose-dependent manner by DEX, which mildly but significantly stimulated production at low concentrations (0.1-10 nM, and inhibited it at 100 nM, while the effects of PRG and RU486 were opposite. HTR-8/SVneo cell invasion of Matrigel was significantly decreased in the presence of DEX and lactose. The obtained data support the proposed regulatory role of steroids in trophoblast gal-1 production.

  13. Alpha Power Modulates Perception Independently of Endogenous Factors

    Directory of Open Access Journals (Sweden)

    Sasskia Brüers

    2018-04-01

    Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

  14. Hormonal modulation of food intake in response to low leptin levels induced by hypergravity

    Science.gov (United States)

    Moran, M. M.; Stein, T. P.; Wade, C. E.

    2001-01-01

    A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  15. Cytokine modulation by stress hormones and antagonist specific hormonal inhibition in rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) head kidney primary cell culture.

    Science.gov (United States)

    Khansari, Ali Reza; Parra, David; Reyes-López, Felipe E; Tort, Lluís

    2017-09-01

    A tight interaction between endocrine and immune systems takes place mainly due to the key role of head kidney in both hormone and cytokine secretion, particularly under stress situations in which the physiological response promotes the synthesis and release of stress hormones which may lead into immunomodulation as side effect. Although such interaction has been previously investigated, this study evaluated for the first time the effect of stress-associated hormones together with their receptor antagonists on the expression of cytokine genes in head kidney primary cell culture (HKPCC) of the freshwater rainbow trout (Oncorhynchus mykiss) and the seawater gilthead sea bream (Sparus aurata). The results showed a striking difference when comparing the response obtained in trout and seabream. Cortisol and adrenocorticotropic hormone (ACTH) decreased the expression of immune-related genes in sea bream but not in rainbow trout and this cortisol effect was reverted by the antagonist mifepristone but not spironolactone. On the other hand, while adrenaline reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6) in rainbow trout, the opposite effect was observed in sea bream showing an increased expression (IL-1β, IL-6). Interestingly, this effect was reverted by antagonist propranolol but not phentolamine. Overall, our results confirm the regional interaction between endocrine and cytokine messengers and a clear difference in the sensitivity to the hormonal stimuli between the two species. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Transcriptome Profiling Reveals the Negative Regulation of Multiple Plant Hormone Signaling Pathways Elicited by Overexpression of C-Repeat Binding Factors

    Directory of Open Access Journals (Sweden)

    Aixin Li

    2017-09-01

    Full Text Available C-repeat binding factors (CBF are a subfamily of AP2 transcription factors that play critical roles in the regulation of plant cold tolerance and growth in low temperature. In the present work, we sought to perform a detailed investigation into global transcriptional regulation of plant hormone signaling associated genes in transgenic plants engineered with CBF genes. RNA samples from Arabidopsis thaliana plants overexpressing two CBF genes, CBF2 and CBF3, were subjected to Illumina HiSeq 2000 RNA sequencing (RNA-Seq. Our results showed that more than half of the hormone associated genes that were differentially expressed in CBF2 or CBF3 transgenic plants were related to auxin signal transduction and metabolism. Most of these alterations in gene expression could lead to repression of auxin signaling. Accordingly, the IAA content was significantly decreased in young tissues of plants overexpressing CBF2 and CBF3 compared with wild type. In addition, genes associated with the biosynthesis of Jasmonate (JA and Salicylic acid (SA, as well as the signal sensing of Brassinolide (BR and SA, were down-regulated, while genes associated with Gibberellin (GA deactivation were up-regulated. In general, overexpression of CBF2 and CBF3 negatively affects multiple plant hormone signaling pathways in Arabidopsis. The transcriptome analysis using CBF2 and CBF3 transgenic plants provides novel and integrated insights into the interaction between CBFs and plant hormones, particularly the modulation of auxin signaling, which may contribute to the improvement of crop yields under abiotic stress via molecular engineering using CBF genes.

  17. Influence of thyroid hormones and transforming growth factor-β1 on cystatin C concentrations.

    Science.gov (United States)

    Kotajima, N; Yanagawa, Y; Aoki, T; Tsunekawa, K; Morimura, T; Ogiwara, T; Nara, M; Murakami, M

    2010-01-01

    Serum cystatin C concentrations are reported to increase in the hyperthyroid state. Serum concentrations of cystatin C and transforming growth factor-β1 (TGF-β1) were measured in patients with thyroid dysfunction, and the effects of 3,5,3'-tri-iodothyronine (T(3)) and TGF-β1 on cystatin C production in human hepatoblastoma (Hep G2) cells were studied. Serum concentrations of cystatin C and TGF-β1 were significantly higher in patients with Graves' disease compared with control subjects. Significantly positive correlations were observed between thyroid hormones and cystatin C, thyroid hormones and TGF-β1, and TGF-β1 and cystatin C in patients with thyroid dysfunction. Serum concentrations of cystatin C and TGF-β1 decreased after treatment for hyperthyroidism. Cystatin C mRNA levels and cystatin C secretion were increased by T(3) and TGF-β1 in cultured Hep G2 cells. These results suggest that serum cystatin C concentrations increase in patients with hyperthyroidism. The mechanisms for this may involve elevation of serum TGF-β1 levels and the stimulatory effects of T(3) and TGF-β1 on cystatin C production.

  18. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men

    NARCIS (Netherlands)

    Watts, Eleanor L; Appleby, Paul N.; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L.; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G.; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A.; Holly, Jeff M P; Hoover, Robert N.; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L.; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S.; Ziegler, Regina G.; Allen, Naomi E.; Key, Timothy J.; Travis, Ruth C.

    2017-01-01

    INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with

  19. Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

    Science.gov (United States)

    Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D

    2017-12-01

    Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable. © 2017 Wiley Periodicals, Inc.

  20. Central Modulation of Neuroinflammation by Neuropeptides and Energy-Sensing Hormones during Obesity

    Directory of Open Access Journals (Sweden)

    Roger Maldonado-Ruiz

    2017-01-01

    Full Text Available Central nervous system (CNS senses energy homeostasis by integrating both peripheral and autonomic signals and responding to them by neurotransmitters and neuropeptides release. Although it is previously considered an immunologically privileged organ, we now know that this is not so. Cells belonging to the immune system, such as B and T lymphocytes, can be recruited into the CNS to face damage or infection, in addition to possessing resident immunological cells, called microglia. In this way, positive energy balance during obesity promotes an inflammatory state in the CNS. Saturated fatty acids from the diet have been pointed out as powerful candidates to trigger immune response in peripheral system and in the CNS. However, how central immunity communicates to peripheral immune response remains to be clarified. Recently there has been a great interest in the neuropeptides, POMC derived peptides, ghrelin, and leptin, due to their capacity to suppress or induce inflammatory responses in the brain, respectively. These may be potential candidates to treat different pathologies associated with autoimmunity and inflammation. In this review, we will discuss the role of lipotoxicity associated with positive energy balance during obesity in proinflammatory response in microglia, B and T lymphocytes, and its modulation by neuropeptides.

  1. Hormonal modulation of novelty processing in women: Enhanced under working memory load with high dehydroepiandrosterone-sulfate-to-dehydroepiandrosterone ratios.

    Science.gov (United States)

    do Vale, Sónia; Selinger, Lenka; Martins, João Martin; Bicho, Manuel; do Carmo, Isabel; Escera, Carles

    2016-11-10

    Several studies have suggested that dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) may enhance working memory and attention, yet current evidence is still inconclusive. The balance between both forms of the hormone might be crucial regarding the effects that DHEA and DHEAS exert on the central nervous system. To test the hypothesis that higher DHEAS-to-DHEA ratios might enhance working memory and/or involuntary attention, we studied the DHEAS-to-DHEA ratio in relation to involuntary attention and working memory processing by recording the electroencephalogram of 22 young women while performing a working memory load task and a task without working memory load in an audio-visual oddball paradigm. DHEA and DHEAS were measured in saliva before each task. We found that a higher DHEAS-to-DHEA ratio was related to enhanced auditory novelty-P3 amplitudes during performance of the working memory task, indicating an increased processing of the distracter, while on the other hand there was no difference in the processing of the visual target. These results suggest that the balance between DHEAS and DHEA levels modulates involuntary attention during the performance of a task with cognitive load without interfering with the processing of the task-relevant visual stimulus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Heterodera schachtii Tyrosinase-like protein a novel nematode effector modulating plant hormone homeostasis

    Czech Academy of Sciences Publication Activity Database

    Habash, S.; Radakovic, Z.S.; Vaňková, Radomíra; Siddique, S.; Dobrev, Petre; Gleason, C.; Grundler, F.M.W.; Elashry, A.

    2017-01-01

    Roč. 7, JUL 31 (2017), č. článku 6874. ISSN 2045-2322 Institutional support: RVO:61389030 Keywords : arabidopsis-thaliana * cyst-nematode * parasitic nematode * transient expression * host plants * sequence * identification * infection * model * transformation Subject RIV: ED - Physiology OBOR OECD: Plant sciences, botany Impact factor: 4.259, year: 2016

  3. Modulation of the hormone setting by Rhodococcus fascians results in ectopic KNOX activation in Arabidopsis

    Czech Academy of Sciences Publication Activity Database

    Depuydt, S.; Doležal, Karel; Van Lijsebettens, M.; Moritz, T.; Holsters, M.; Vereecke, D.

    2008-01-01

    Roč. 146, č. 3 (2008), s. 1267-1281 ISSN 0032-0889 Institutional research plan: CEZ:AV0Z50380511 Keywords : KNOTTED1-LIKE HOMEOBOX GENE * CYTOKININ BIOSYNTHESIS * MERISTEM ACTIVITY Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.110, year: 2008

  4. 7-Rhamnosylated Flavonols Modulate Homeostasis of the Plant Hormone Auxin and Affect Plant Development

    Czech Academy of Sciences Publication Activity Database

    Kuhn, B.M.; Errafi, S.; Bucher, R.; Dobrev, Petre; Geisler, M.; Bigler, L.; Zažímalová, Eva; Ringli, Ch.

    2016-01-01

    Roč. 291, č. 10 (2016), s. 5385-5395 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GAP305/11/0797 Institutional support: RVO:61389030 Keywords : Arabidopsis thaliana * auxin * flavonoid Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.125, year: 2016

  5. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ding, Ming; Jensen, Charlotte H

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which is a member of the Notch-Delta family. We previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene transfer procedure. We found that increased serum FA1 levels led to a significant reduction in total body weight, fat...... mass, and bone mass in a dose-dependent manner. Reduced bone mass in FA1 mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58 and 72%, respectively. Because FA1 is colocalized with GH in the pituitary gland, we explored the possible modulation of serum FA1...

  6. The ABA-INSENSITIVE-4 (ABI4) transcription factor links redox, hormone and sugar signaling pathways.

    Science.gov (United States)

    Foyer, Christine H; Kerchev, Pavel I; Hancock, Robert D

    2012-02-01

    The cellular reduction-oxidation (redox) hub processes information from metabolism and the environment and so regulates plant growth and defense through integration with the hormone signaling network. One key pathway of redox control involves interactions with ABSCISIC ACID (ABA). Accumulating evidence suggests that the ABA-INSENSITIVE-4 (ABI4) transcription factor plays a key role in transmitting information concerning the abundance of ascorbate and hence the ability of cells to buffer oxidative challenges. ABI4 is required for the ascorbate-dependent control of growth, a process that involves enhancement of salicylic acid (SA) signaling and inhibition of jasmonic acid (JA) signaling pathways. Low redox buffering capacity reinforces SA- JA- interactions through the mediation of ABA and ABI4 to fine-tune plant growth and defense in relation to metabolic cues and environmental challenges. Moreover, ABI4-mediated pathways of sugar sensitivity are also responsive to the abundance of ascorbate, providing evidence of overlap between redox and sugar signaling pathways.

  7. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders

    2008-01-01

    compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM......Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...... investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six...

  8. Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus: Influential Factors and Reference Intervals.

    Directory of Open Access Journals (Sweden)

    Leslie B Hart

    Full Text Available Inshore common bottlenose dolphins (Tursiops truncatus are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone that account for the influence of intrinsic (e.g., age, sex and extrinsic (e.g., time factors. Ultimately, these reference intervals will be used to gauge an individual's response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000-2012. Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05, and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91-4.21 µg/dL and following biological sampling aboard a research vessel (95% RI: 2.32-6.68 µg/dL. To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34 had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time were not observed in the current project (p<0.05. Also, approximately 16% of

  9. Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential Factors and Reference Intervals.

    Science.gov (United States)

    Hart, Leslie B; Wells, Randall S; Kellar, Nick; Balmer, Brian C; Hohn, Aleta A; Lamb, Stephen V; Rowles, Teri; Zolman, Eric S; Schwacke, Lori H

    2015-01-01

    Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs) for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone) that account for the influence of intrinsic (e.g., age, sex) and extrinsic (e.g., time) factors. Ultimately, these reference intervals will be used to gauge an individual's response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs) were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000-2012). Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05), and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91-4.21 µg/dL) and following biological sampling aboard a research vessel (95% RI: 2.32-6.68 µg/dL). To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34) had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time) were not observed in the current project (p<0.05). Also, approximately 16% of Sarasota Bay

  10. Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective.

    Science.gov (United States)

    Figlewicz, Dianne P

    2015-01-01

    Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention.

  11. Risk Factors for Eating Disorder Psychopathology within the Treatment Seeking Transgender Population: The Role of Cross-Sex Hormone Treatment.

    Science.gov (United States)

    Jones, Bethany Alice; Haycraft, Emma; Bouman, Walter Pierre; Brewin, Nicola; Claes, Laurence; Arcelus, Jon

    2018-03-01

    Many transgender people experience high levels of body dissatisfaction, which is one of the numerous factors known to increase vulnerability to eating disorder symptoms in the cisgender (non-trans) population. Cross-sex hormones can alleviate body dissatisfaction so might also alleviate eating disorder symptoms. This study aimed to explore risk factors for eating disorder symptoms in transgender people and the role of cross-sex hormones. Individuals assessed at a national transgender health service were invited to participate (N = 563). Transgender people not on cross-sex hormones reported higher levels of eating disorder psychopathology than people who were. High body dissatisfaction, perfectionism, anxiety symptoms, and low self-esteem were risk factors for eating psychopathology, but, after controlling for these, significant differences in eating psychopathology between people who were and were not on cross-sex hormones disappeared. Cross-sex hormones may alleviate eating disorder psychopathology. Given the high prevalence of transgender identities, clinicians at eating disorder services should assess for gender identity issues. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

  12. The effect of thyroid hormone and bone metablism-associated growth factor on the patients of hyperthyreosis

    International Nuclear Information System (INIS)

    Chen Wenhan; Xie Rongxing; Chen Shaozhu

    2008-01-01

    Objective: To evaluate the effect of high concentration of thyroid hormone and cell growth factor content on the bone metabolism of hyperthyreosis. Methods: Radiation immunological test and chemiluminescence methods are employed to determinate the content of free triiodothyronine (FT 3 ), free thyroxine (FT 4 ), thyroid stimulating hormone (TSH), insulin-like growth factor II(IGF-II), calcitonic (CT), interleukin-6 (IL-6) and tumor necrosis factor (TNF) of serum in health adult and parts of hyperthyreosis patients. Results: Hyperthyreosis patients have a higher content of FT 4 , FT 3 and IL-6 than those of health adult (t was 16.69,11.33,7.92, respectively, P<0.01), while the content of TSH, IGF-II, CT, TNF are obvious decreasing (t was 13.08, 8.34, 5.29, 8.75, respectively, P<0.01). Conclusion: In patients with hyperthyreosis, high concentration thyroid hormone cause accentuation of protein metabolism, decrease calcium homeostasis by disorders of phosphorus and calcium metabolism, high concentration thyroid hormone and low level CT resulted in bone loss. Decreased ICF-II may be the main cause of osteoporosis as the result of high concentration thyroid hormone. (authors)

  13. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

    Science.gov (United States)

    Lang, Charles H; Frost, Robert A

    2002-05-01

    The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

  14. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    International Nuclear Information System (INIS)

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-01-01

    The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

  15. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-I...

  16. Insulin-like growth factor 1 (IGF-1): a growth hormone

    Science.gov (United States)

    Laron, Z

    2001-01-01

    Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process. Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice. Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year. Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH. PMID:11577173

  17. Neuroendocrine and Cardiovascular Risk Factors in Adults with Pituitary Growth Hormone Deficiency (Literature Review

    Directory of Open Access Journals (Sweden)

    S.I. Ismailov

    2013-08-01

    Full Text Available In this article authors discussed the results of literature review, which has been dedicated to study of different complications of growth hormone deficiency in adults, referring to the literature of the last 10–15 years. Based on this analysis, the authors concluded that in adults with growth hormone deficiency there is an adverse profile of cardiovascular risk. Patients with growth hormone deficiency have an adverse lipid profile, elevated body mass index, increased waist circumference and a high risk of hypertension. These disorders are likely to explain the increased cardiovascular mortality observed in patients with hypopituitarism, regardless of the etiology of growth hormone deficiency in adults.

  18. Thyroid hormone interacts with the sympathetic nervous system to modulate bone mass and structure in young adult mice.

    Science.gov (United States)

    Fonseca, Tatiana L; Teixeira, Marilia B C G; Miranda-Rodrigues, Manuela; Rodrigues-Miranda, Manuela; Silva, Marcos V; Martins, Gisele M; Costa, Cristiane C; Arita, Danielle Y; Perez, Juliana D; Casarini, Dulce E; Brum, Patricia C; Gouveia, Cecilia H A

    2014-08-15

    To investigate whether thyroid hormone (TH) interacts with the sympathetic nervous system (SNS) to modulate bone mass and structure, we studied the effects of daily T3 treatment in a supraphysiological dose for 12 wk on the bone of young adult mice with chronic sympathetic hyperactivity owing to double-gene disruption of adrenoceptors that negatively regulate norepinephrine release, α(2A)-AR, and α(2C)-AR (α(2A/2C)-AR(-/-) mice). As expected, T3 treatment caused a generalized decrease in the areal bone mineral density (aBMD) of WT mice (determined by DEXA), followed by deleterious effects on the trabecular and cortical bone microstructural parameters (determined by μCT) of the femur and vertebra and on the biomechanical properties (maximum load, ultimate load, and stiffness) of the femur. Surprisingly, α(2A/2C)-AR(-/-) mice were resistant to most of these T3-induced negative effects. Interestingly, the mRNA expression of osteoprotegerin, a protein that limits osteoclast activity, was upregulated and downregulated by T3 in the bone of α(2A/2C)-AR(-/-) and WT mice, respectively. β1-AR mRNA expression and IGF-I serum levels, which exert bone anabolic effects, were increased by T3 treatment only in α(2A/2C)-AR(-/-) mice. As expected, T3 inhibited the cell growth of calvaria-derived osteoblasts isolated from WT mice, but this effect was abolished or reverted in cells isolated from KO mice. Collectively, these findings support the hypothesis of a TH-SNS interaction to control bone mass and structure of young adult mice and suggests that this interaction may involve α2-AR signaling. Finally, the present findings offer new insights into the mechanisms through which TH regulates bone mass, structure, and physiology. Copyright © 2014 the American Physiological Society.

  19. Reciprocal modulation of internal and external factors determines individual movements.

    Science.gov (United States)

    Martin, Jodie; van Moorter, Bram; Revilla, Eloy; Blanchard, Pierrick; Dray, Stéphane; Quenette, Pierre-Yves; Allainé, Dominique; Swenson, Jon E

    2013-03-01

    Movement is fundamental to individual and population dynamics, as it allows individuals to meet their basic requirements. Although movement patterns reflect interactions between internal and external factors, only few studies have examined the effects of these factors on movement simultaneously, and they generally focused on particular biological contexts (e.g. dispersal, foraging). However, the relative importance of these factors in driving individual routine movements might reflect a species' potential flexibility to cope with landscape changes and therefore buffer their potential impact on fitness. We used data from GPS collars on Scandinavian brown bears to investigate the relative role of these factors, as well as an additional factor (period of the year) on routine movements at two spatial scales (hourly and daily relocations). As expected, internal factors played a major role in driving movement, compared to external factors at both scales, but its relative importance was greater at a finer scale. In particular, the interaction between reproductive status and period of the year was one of the most influential variables, females being constrained by the movement capacity of their cubs in the first periods of the year. The effect of human disturbance on movement was also greater for females with cubs than for lone females. This study showed how reciprocal modulation of internal and external factors is shaping space use of brown bears. We stress that these factors should be studied simultaneously to avoid the risk of obtaining context-dependent inferences. Moreover, the study of their relative contribution is also highly relevant in the context of multiple-use landscapes, as human activities generally affect the landscape more than they affect the internal states of an individual. Species or individuals with important internal constraints should be less responsive to changes in their environment as they have less freedom from internal constraints and should

  20. Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti

    Science.gov (United States)

    2013-01-01

    Background Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week. Results In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin. Conclusions These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties. PMID:23394545

  1. Changes of plasma growth hormone, insulin-like growth factors-I, thyroid hormones, and testosterone concentrations in embryos and broiler chickens incubated under monochromatic green light

    Directory of Open Access Journals (Sweden)

    Lin Zhang

    2014-07-01

    Full Text Available Previous studies showed that monochromatic green light stimuli during embryogenesis accelerated posthatch body weight and pectoral muscle growth of broilers. In this experiment, we further investigated whether the regulation of broiler embryonic or posthatch growth by green light stimulus during incubation is associated with the changes of some important hormones at different ages of embryos and broiler chickens. Fertile broiler eggs (Arbor Acres, n=880 were pre-weighed and randomly assigned 1 of 2 incubation treatment groups: i dark condition (control group, and ii monochromatic green light group (560 nm. The monochromatic lighting systems sourced from light-emitting diode lamps were equalised at the intensity of 15 lux (lx at eggshell level. The dark condition was set as a commercial control from day one until hatching. After hatch, 120 day-old male chicks from each group were housed under white light with an intensity of 30 lx at bird-head level. Compared with the dark condition, chicks incubated under the green light showed significantly higher growth hormone (GH levels from 19 d of embryogenesis (E19 to 5 d of posthatch (H5, and higher plasma insulinlike growth factor (IGF-I levels from both E17 to E19 and H3 to H35. No significant differences were found in plasma thyroxine, triiodothyronine, and testosterone in embryos or hatched birds between the 2 groups. These results indicate that somatotropic axis hormones (GH and IGF-I may be the most important contributor to chicken growth promoted by green light stimuli during embryogenesis.

  2. Understanding Risky Behavior: The Influence of Cognitive, Emotional and Hormonal Factors on Decision-Making under Risk

    OpenAIRE

    Kusev, Petko; Purser, Harry; Heilman, Renata; Cooke, Alex J.; Van Schaik, Paul; Baranova, Victoria; Martin, Rose; Ayton, Peter

    2017-01-01

    Financial risky decisions and evaluations pervade many human everyday activities. Scientific research in such decision-making typically explores the influence of socio-economic and cognitive factors on financial behavior. However, very little research has explored the holistic influence of contextual, emotional, and hormonal factors on preferences for risk in insurance and investment behaviors. Accordingly, the goal of this review article is to address the complexity of individual risky behav...

  3. Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

    International Nuclear Information System (INIS)

    Ritte, Rebecca; Grote, Verena; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Berrino, Franco; Mattiello, Amalia; Tumino, Rosario; Tikk, Kaja; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, H Bas; Gils, Carla H van; Peeters, Petra HM; Lukanova, Annekatrin; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Tjønneland, Anne; Rinaldi, Sabina; Vineis, Paulo; Merritt, Melissa A; Riboli, Elio; Kaaks, Rudolf; Olsen, Anja; Overvad, Kim; Dossus, Laure; Fournier, Agnès; Clavel-Chapelon, Françoise

    2013-01-01

    The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p trend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p trend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p het = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant

  4. Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

    Science.gov (United States)

    Schenke, S; Klett, R; Braun, S; Zimny, M

    2013-01-01

    Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

  5. Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia.

    Science.gov (United States)

    McCall-Hosenfeld, Jennifer S; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

    2003-04-01

    To determine activity of the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis in women with fibromyalgia (FM). Premenopausal women with FM (n = 24) and premenopausal healthy women (n = 27) were studied. IGF-1 was measured in 23 patients with FM and 25 controls. GH was measured during a stepped hypoglycemic hyperinsulinemic clamp procedure (blood glucose decreased from 90 to 40 mg/dl every 30 min in 10 mg/dl decrements) in 12 FM and 13 control subjects. IGF-1 concentrations were similar in the FM (200 +/- 71 ng/ml, mean +/- SD) and control (184 +/- 70 ng/ml) groups. By multiple variable analysis, IGF-1 was negatively associated with age (p = 0.0006), body mass index (BMI) (p = 0.006), and 24 h urinary free cortisol (p = 0.007) in healthy controls. Even after accounting for these factors, there was no association between FM and IGF-1. The average peak GH achieved during hypoglycemia was lower in patients with FM (range 5 to 58 ng/ml, median 13 ng/ml) versus controls (6 to 68 ng/ml, median 21 ng/ml) (p = 0.04). However, BMI was a significant predictor of average peak GH in FM (r = -0.62, p BMI, there was no significant association between FM subjects and the average peak GH (p = 0.20). In this sample of premenopausal women with FM, the activity of the GH-IGF-1 axis was similar to that of healthy controls. Increases in age and obesity were both strongly associated with lower activity of this axis, suggesting that these factors must be considered when studying activity of the GH-IGF-1 axis in FM.

  6. The effects of hormones and physical exercise on hippocampal structural plasticity.

    Science.gov (United States)

    Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

    2016-04-01

    The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Plasma growth hormone response to human growth hormone releasing factor in rats administered with chlorpromazine and antiserum against somatostatin. Effects of hypo- and hyperthyroidism.

    Science.gov (United States)

    Wakabayashi, I; Tonegawa, Y; Ihara, T; Hattori, M; Shibasaki, T; Ling, N

    1985-10-01

    The effect of hypo- and hyperthyroidism on the plasma growth hormone (GH) response to synthetic human growth hormone releasing factor (GRF) was determined in conscious, freely moving rats pretreated with chlorpromazine and antiserum against somatostatin. Chlorpromazine plus somatostatin antiserum pretreated rats gave consistent response to GRF which was not observed in untreated rats. Chlorpromazine alone has no effect on GH secretion induced by GRF in rat pituitary monolayer culture. In rats made hypothyroid by thyroidectomy, both basal and peak plasma GH responses to a small (0.25 microgram/kg bw) and a moderate dose of GRF (1 microgram/kg bw) were significantly reduced as compared to controls. In rats made hyperthyroid by the administration of thyroxine, basal and peak plasma GH responses to a small but not to a moderate dose of GRF were significantly reduced as compared to controls. A reduced plasma GH response to a small dose of GRF was observed 8 days after the cessation of thyroxine administration. The pituitary GH reserve was markedly reduced in hypothyroid but not in hyperthyroid rats as compared to their respective controls. These results indicate that plasma GH response to GRF is reduced both in hypo- and hyperthyroidism. The mechanism involved in the phenomenon appears to be different between the two conditions.

  8. Growth hormone and insulin-like growth factor 1 affect the severity of Graves' disease.

    Science.gov (United States)

    Di Cerbo, Alfredo; Pezzuto, Federica; Di Cerbo, Alessandro

    2017-01-01

    Graves' disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves' disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves' disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves' disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves' disease and synergize the stimulatory activity of Graves' IgGs. Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.The coexistence of acromegaly and Graves' disease is a very unusual event, the prevalence being Graves' disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves' disease.

  9. Circadian System and Melatonin Hormone: Risk Factors for Complications during Pregnancy

    Directory of Open Access Journals (Sweden)

    F. J. Valenzuela

    2015-01-01

    Full Text Available Pregnancy is a complex and well-regulated temporal event in which several steps are finely orchestrated including implantation, decidualization, placentation, and partum and any temporary alteration has serious effects on fetal and maternal health. Interestingly, alterations of circadian rhythms (i.e., shiftwork have been correlated with increased risk of preterm delivery, intrauterine growth restriction, and preeclampsia. In the last few years evidence is accumulating that the placenta may have a functional circadian system and express the clock genes Bmal1, Per1-2, and Clock. On the other hand, there is evidence that the human placenta synthesizes melatonin, hormone involved in the regulation of the circadian system in other tissues. Moreover, is unknown the role of this local production of melatonin and whether this production have a circadian pattern. Available information indicates that melatonin induces in placenta the expression of antioxidant enzymes catalase and superoxide dismutase, prevents the injury produced by oxidative stress, and inhibits the expression of vascular endothelial growth factor (VEGF a gene that in other tissues is controlled by clock genes. In this review we aim to analyze available information regarding clock genes and clock genes controlled genes such as VEGF and the possible role of melatonin synthesis in the placenta.

  10. The AP2/ERF Transcription Factor DRNL Modulates Gynoecium Development and Affects Its Response to Cytokinin

    Directory of Open Access Journals (Sweden)

    Yolanda Durán-Medina

    2017-10-01

    Full Text Available The gynoecium is the female reproductive system in flowering plants. It is a complex structure formed by different tissues, some that are essential for reproduction and others that facilitate the fertilization process and nurture and protect the developing seeds. The coordinated development of these different tissues during the formation of the gynoecium is important for reproductive success. Both hormones and genetic regulators guide the development of the different tissues. Auxin and cytokinin in particular have been found to play important roles in this process. On the other hand, the AP2/ERF2 transcription factor BOL/DRNL/ESR2/SOB is expressed at very early stages of aerial organ formation and has been proposed to be a marker for organ founder cells. In this work, we found that this gene is also expressed at later stages during gynoecium development, particularly at the lateral regions (the region related to the valves of the ovary. The loss of DRNL function affects gynoecium development. Some of the mutant phenotypes present similarities to those observed in plants treated with exogenous cytokinins, and AHP6 has been previously proposed to be a target of DRNL. Therefore, we explored the response of drnl-2 developing gynoecia to cytokinins, and found that the loss of DRNL function affects the response of the gynoecium to exogenously applied cytokinins in a developmental-stage-dependent manner. In summary, this gene participates during gynoecium development, possibly through the dynamic modulation of cytokinin homeostasis and response.

  11. Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning.

    Science.gov (United States)

    das Neves de Araújo Lima, Emeline; Barbosa, Natália Guimarães; Dos Santos, Ana Celly Souza; AraújoMouraLemos, Telma Maria; de Souza, Cleber Machado; Trevilatto, Paula Cristina; da Silveira, Ericka Janine Dantas; de Medeiros, Ana Miryam Costa

    2016-09-01

    The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. Cross sectional study. Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo

    Science.gov (United States)

    Colvin, Stephanie C.; Malik, Raleigh E.; Showalter, Aaron D.; Sloop, Kyle W.; Rhodes, Simon J.

    2011-01-01

    The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable. PMID:21149718

  13. Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

    Science.gov (United States)

    Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

  14. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

    Directory of Open Access Journals (Sweden)

    T.S. de Melo

    Full Text Available Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group were fed a normal diet (ND or HFD, treated orally or not with either FA (10 mg/kg or sibutramine (10 mg/kg for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCH-1 were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05 decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05 reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05 inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

  15. Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential Factors and Reference Intervals

    OpenAIRE

    Hart, Leslie B.; Wells, Randall S.; Kellar, Nick; Balmer, Brian C.; Hohn, Aleta A.; Lamb, Stephen V.; Rowles, Teri; Zolman, Eric S.; Schwacke, Lori H.

    2015-01-01

    Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs) for adren...

  16. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

    Science.gov (United States)

    Zhou, Bin; Honor, Leah B.; He, Huamei; Ma, Qing; Oh, Jin-Hee; Butterfield, Catherine; Lin, Ruei-Zeng; Melero-Martin, Juan M.; Dolmatova, Elena; Duffy, Heather S.; von Gise, Alexander; Zhou, Pingzhu; Hu, Yong Wu; Wang, Gang; Zhang, Bing; Wang, Lianchun; Hall, Jennifer L.; Moses, Marsha A.; McGowan, Francis X.; Pu, William T.

    2011-01-01

    The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection. PMID:21505261

  17. The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

    Science.gov (United States)

    Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

    2015-01-01

    The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

  18. Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

    Science.gov (United States)

    Clifton, Kari B; Conover, Cheryl A

    2015-12-01

    Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels

    Directory of Open Access Journals (Sweden)

    In Hyuk Chung

    2014-06-01

    Full Text Available PurposeThis study was performed to investigate the relationship between serum vitamin D and parathyroid hormone (PTH levels as well as to describe the prevalence and the risk factors of vitamin D deficiency (VDD in Korean children.MethodsParticipants were 1,212 children aged 4 to 15 years, who visited Bundang CHA Medical Center (located at 37°N between March 2012 and February 2013. Overweight was defined as body mass index≥85th percentile. Participants were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25-hydroxyvitamin D (25OHD <20 ng/mL.ResultsThe level of 25OHD was significantly lower in overweight group than in normal weight group (17.1±5.1 ng/mL vs. 19.1±6.1 ng/mL, P<0.001. Winter-spring season (odds ratio [OR], 4.46; 95% confidence interval [CI], 3.45-5.77, older age group (OR, 1.60; 95% CI, 1.36-1.88, and overweight (OR, 2.21; 95% CI, 1.62-3.01 were independently related with VDD. The PTH levels were significantly higher in VDD group compared to vitamin D insufficiency and sufficiency group (P<0.001. In normal weight children, 25OHD (β=-0.007, P<0.001 and ionized calcium (β=-0.594, P=0.007 were independently related with PTH, however, these associations were not significant in overweight children.ConclusionVDD is very common in Korean children and its prevalence increases in winter-spring season, in overweight children and in older age groups. Further investigation on the vitamin D and PTH metabolism according to adiposity is required.

  20. The effect of combined exercise training on plasma Leptin levels and hormonal factors in overweight men

    Directory of Open Access Journals (Sweden)

    saeed Emamdost

    2014-06-01

    Full Text Available Background: The purpose of this study was to determine the effect of a period of combined exercise training on the plasma leptin level and hormonal factors in overweight men.   Materials and Methods: The subjects of this research consisted of thirty males (22-42 years old, BMI ≥29 who randomly were divided into experimental (n=15 and control groups(n=15. The experimental group performed for 8 weeks aerobic and resistance training, 3 sessions per week and each session included 10-12 station strength training at 75-70% of One Repetition Maximum (1RM for the first 4 weeks and at 75-80% of 1RM for the second 4 weeks. At the end, 10 minutes aerobic runing training at 70-75% of MHR in the first 4 weeks and 13 minute at 75-80% of MHR in the second 4 weeks were conducted.   Results: Leptin, body weight, Body Mass Index (BMI and insulin significantly decreased after the training ((P<0.05. However, There were no significant differences in the serum levels of cortisol and testosteron after 8 weeks concurrent training. The ratio of testosteron to cortisol (T/C in the experimental group showed a slight increase.   Conclusion: Generally, it appears that decrease of leptin due to a period of combined exercise training is more associated with reduce of body fat, weight and BMI than the change of testosteron or cortisol. In contrast to most researches, it seems that combined exercise training is more effective.

  1. Normal epidermal growth factor receptor signaling is dispensable for bone anabolic effects of parathyroid hormone.

    Science.gov (United States)

    Schneider, Marlon R; Dahlhoff, Maik; Andrukhova, Olena; Grill, Jessica; Glösmann, Martin; Schüler, Christiane; Weber, Karin; Wolf, Eckhard; Erben, Reinhold G

    2012-01-01

    Although the bone anabolic properties of intermittent parathyroid hormone (PTH) have long been employed in the treatment of osteoporosis, the molecular mechanisms behind this action remain largely unknown. Previous studies showed that PTH increases the expression and the activity of epidermal growth factor receptor (EGFR) in osteoblasts, and activation of ERK1/2 by PTH in osteoblasts was demonstrated to induce the proteolytical release of EGFR ligands and EGFR transactivation. However, conclusive evidence for an important role of the EGFR system in mediating the anabolic actions of intermittent PTH on bone in vivo is lacking. Here, we evaluated the effects of intermittent PTH on bone in Waved-5 (Wa5) mice which carry an antimorphic Egfr allele whose product acts as a dominant negative receptor. Heterozygous Wa5 females and control littermates received a subcutaneous injection of PTH (80 μg/kg) or buffer on 5 days per week for 4 weeks. Wa5 mice had slightly lower total bone mineral density (BMD), but normal cancellous bone volume and turnover in the distal femoral metaphysis. The presence of the antimorphic Egfr allele neither influenced the PTH-induced increase in serum osteocalcin nor the increases in distal femoral BMD, cortical thickness, cancellous bone volume, and cancellous bone formation rate. Similarly, the PTH-induced rise in lumbar vertebral BMD was unchanged in Wa5 relative to wild-type mice. Wa5-derived osteoblasts showed considerably lower basal extracellular signal-regulated kinase 1/2 (ERK1/2) activation as compared to control osteoblasts. Whereas activation of ERK1/2 by the EGFR ligand amphiregulin was largely blocked in Wa5 osteoblasts, treatment with PTH induced ERK1/2 activation comparable to that observed in control osteoblasts, relative to baseline levels. Our data indicate that impairment of EGFR signaling does not affect the anabolic action of intermittent PTH on cancellous and cortical bone. Copyright © 2011. Published by Elsevier Inc.

  2. Growth hormone and insulin-like growth factor 1 secretions in eating disorders: Correlations with psychopathological aspects of the disorders.

    Science.gov (United States)

    Brambilla, Francesca; Santonastaso, Paolo; Caregaro, Lorenza; Favaro, Angela

    2018-05-01

    Hormonal alterations in Eating Disorders (ED) may result from the biochemical stress of malnutrition/starvation. The correlations between some hormonal impairments, particularly of the somatotropic axis, and the psychopathological aspects of ED are still undefined. We measured the plasma concentrations of the somatotropic hormone (GH) and the insulin-like growth factor-1 (IGF-1) in 136 patients with various forms of ED, 65 with restricted Anorexia Nervosa (ANR), 19 with bingeing-purging Anorexia Nervosa (ANBP), 12 with purging-non binging Anorexia Nervosa (ANP), 26 with Bulimia Nervosa (BN), 8 with ED not otherwise specified-anorexic type (EDNOS-AN), 7 with ED not otherwise specified-bulimic type (EDNOS-BN) and in 30 healthy controls. Psychological assessment of patients and controls was performed using two outpatient rating scales, the Eating Disorder Inventory-2 (EDI-2) and the Symptom Checklist-90 (SCL-90). Significant negative or positive correlations were observed between GH-IGF-1 concentrations and impairments on several EDI-2 subscales (drive for thinness, body dissatisfaction, interoceptive awareness, sense of ineffectiveness, interpersonal distrust, maturity fear) and on SCL-90 subitems (depression, hostility, obsessivity compulsivity, anxiety), suggesting a possible hormonal modulatory effect on specific aspects of ED psychopathology. Copyright © 2017. Published by Elsevier B.V.

  3. Understanding Risky Behavior: The Influence of Cognitive, Emotional and Hormonal Factors on Decision-Making under Risk

    Science.gov (United States)

    Kusev, Petko; Purser, Harry; Heilman, Renata; Cooke, Alex J.; Van Schaik, Paul; Baranova, Victoria; Martin, Rose; Ayton, Peter

    2017-01-01

    Financial risky decisions and evaluations pervade many human everyday activities. Scientific research in such decision-making typically explores the influence of socio-economic and cognitive factors on financial behavior. However, very little research has explored the holistic influence of contextual, emotional, and hormonal factors on preferences for risk in insurance and investment behaviors. Accordingly, the goal of this review article is to address the complexity of individual risky behavior and its underlying psychological factors, as well as to critically examine current regulations on financial behavior. PMID:28203215

  4. Understanding Risky Behavior: The Influence of Cognitive, Emotional and Hormonal Factors on Decision-Making under Risk.

    Science.gov (United States)

    Kusev, Petko; Purser, Harry; Heilman, Renata; Cooke, Alex J; Van Schaik, Paul; Baranova, Victoria; Martin, Rose; Ayton, Peter

    2017-01-01

    Financial risky decisions and evaluations pervade many human everyday activities. Scientific research in such decision-making typically explores the influence of socio-economic and cognitive factors on financial behavior. However, very little research has explored the holistic influence of contextual, emotional, and hormonal factors on preferences for risk in insurance and investment behaviors. Accordingly, the goal of this review article is to address the complexity of individual risky behavior and its underlying psychological factors, as well as to critically examine current regulations on financial behavior.

  5. Inhibition of Follicle-Stimulating Hormone-Induced Preovulatory Follicles in Rats Treated with a Nonsteroidal Negative Allosteric Modulator of Follicle-Stimulating Hormone Receptor1

    OpenAIRE

    Dias, James A.; Campo, Brice; Weaver, Barbara A.; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M.; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M.

    2013-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human F...

  6. Transcription elongation factors are involved in programming hormone production in pituitary neuroendocrine GH4C1 cells.

    Science.gov (United States)

    Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

    2010-05-05

    Transcription elongation of many eukaryotic genes is regulated. Two negative transcription elongation factors, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) are known to stall collaboratively RNA polymerase II promoter proximally. We discovered that DSIF and NELF are linked to hormone expression in rat pituitary GH4C1 cells. When NELF-E, a subunit of NELF or Spt5, a subunit of DSIF was stably knocked-down, prolactin (PRL) expression was increased both at the mRNA and protein levels. In contrast, stable knock-down of only Spt5 abolished growth hormone (GH) expression. Transient NELF-E knock-down increased coincidentally PRL expression and enhanced transcription of a PRL-promoter reporter gene. However, no direct interaction of NELF with the PRL gene could be demonstrated by chromatin immuno-precipitation. Thus, NELF suppressed PRL promoter activity indirectly. In conclusion, transcription regulation by NELF and DSIF is continuously involved in the control of hormone production and may contribute to neuroendocrine cell differentiation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.

    Science.gov (United States)

    van Beveren, N J M; Schwarz, E; Noll, R; Guest, P C; Meijer, C; de Haan, L; Bahn, S

    2014-08-26

    Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.

  8. Digoxin-like immunoreactivity, endogeneous cardiac glycoside-like factors (s) and natriuretic hormone

    International Nuclear Information System (INIS)

    Clerico, A.

    1987-01-01

    Endogenous factors crossreacting with antidigoxin antibodies (digoxin-like immunoreactive substances=DLIS) have been found in several tissues and body fluids of animals and humans, using commercially avaiable digoxin RIA or EIA methods. Detectable DLIS concentration were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that DLIS could be a substance with low molecular weight. Experimental studies and theoretical consideration suggest that DLIS, in addition to reacting with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na + /K + ATPase (sodium pump). Therefore, it has been suggested that DLSI is an endogeneous modulator of the membrane sodium-potassium pump and it could play a role in the regulation of fluid and electrolytes muscular tone of myocardial and also in pathogenesis of hypertension

  9. Hormone therapy modulates ET(A) mRNA expression in the aorta of ovariectomised New Zealand White rabbits

    DEFF Research Database (Denmark)

    Pedersen, Susan Helene; Nielsen, Lars Bo; Pedersen, Nina Gros

    2009-01-01

    OBJECTIVE: To study the effect of 17beta-estradiol (E(2)) or conjugated equine estrogens (CEE) alone and in combination with norethisterone acetate (NETA) or medroxyprogesterone acetate (MPA) on the endothelin-1 (ET-1) system. METHODS: New Zealand White rabbits were treated with E(2), CEE, E(2......(A) receptor. The effect was maintained with the co-administration of NETA, but not MPA. The differential effects of specific hormone components may explain the variable effects of hormone therapy on the arterial wall....

  10. Modulation by steroid hormones of a ''sexy'' acoustic signal in an Oscine species, the Common Canary Serinus canaria

    Directory of Open Access Journals (Sweden)

    Rybak Fanny

    2004-01-01

    Full Text Available The respective influence of testosterone and estradiol on the structure of the Common Canary Serinus canaria song was studied by experimentally controlling blood levels of steroid hormones in males and analyzing the consequent effects on acoustic parameters. A detailed acoustic analysis of the songs produced before and after hormonal manipulation revealed that testosterone and estradiol seem to control distinct song parameters independently. The presence of receptors for testosterone and estradiol in the brain neural pathway controlling song production strongly suggests that the observed effects are mediated by a steroid action at the neuronal level.

  11. Modulation by steroid hormones of a "sexy" acoustic signal in an Oscine species, the Common Canary Serinus canaria.

    Science.gov (United States)

    Rybak, Fanny; Gahr, Manfred

    2004-06-01

    The respective influence of testosterone and estradiol on the structure of the Common Canary Serinus canaria song was studied by experimentally controlling blood levels of steroid hormones in males and analyzing the consequent effects on acoustic parameters. A detailed acoustic analysis of the songs produced before and after hormonal manipulation revealed that testosterone and estradiol seem to control distinct song parameters independently. The presence of receptors for testosterone and estradiol in the brain neural pathway controlling song production strongly suggests that the observed effects are mediated by a steroid action at the neuronal level.

  12. Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity.

    Science.gov (United States)

    Laron, Zvi

    2002-01-01

    Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

  13. Growth hormone-insuline-like growth factor-I system in pejerrey Odontesthes bonariensis (Atheriniformes

    Directory of Open Access Journals (Sweden)

    S.E. Arranz

    2008-07-01

    Full Text Available Using biotechnology to increase the growth rates of fish is likely to reduce production costs per unit of food. Among vertebrates, fish appear to occupy a unique position, when growth patterns are considered. With few exceptions, fish species tend to grow indeterminately, implying that size is never fixed. Both hyperplasia and hypertrophy contribute to post-larval muscle growth in fish. Growth hormone (GH - Insulin-like Growth Factor I (IGF-I is the most important growth axis in fish. Our experimental model, the pejerrey, Odontesthes bonariensis (Ateriniformes is a South American inland water fish considered to be a promising species for intensive aquaculture. However, one major drawback to achieve this goal is its slow growth in captivity. In order to understand how growth is regulated in this species, our first objective was to characterized pejerrey GH- IGF-I axis. We first cloned and characterized pejerrey (pj GH, IGF-I and the growth hormone receptors (GHRs I and II. In addition to providing valuable data for evolutionary comparison of GH, investigation of GH action in teleosts is particularly important because of its potential application in aquaculture. GH can not only promote the somatic growth in fish but also lower dietary protein requirements. A prerequisite for providing sufficient amounts of GH for basic research and aquaculture application is a large-scale production of GH. For that purpose, recombinant pjGH was expressed in a bacterial system. Protocols for solubilization and proper folding were achieved. Activity of recombinant pjGH was assessed in fish by measuring the liver IGF-I response to different doses of GH. IGF-I transcript was measured in the liver after pjGHr in vivo stimulation by means of quantitative real-time PCR assays. A dose-dependent response of IGF-I mRNA was observed after pjGHr administration, and reached a 6 fold IGF-I maximum increase over control group when 2.5 µg pjGH /g-body weight were injected

  14. Hormone abuse in sports: the antidoping perspective.

    Science.gov (United States)

    Barroso, Osquel; Mazzoni, Irene; Rabin, Olivier

    2008-05-01

    Since ancient times, unethical athletes have attempted to gain an unfair competitive advantage through the use of doping substances. A list of doping substances and methods banned in sports is published yearly by the World Anti-Doping Agency (WADA). A substance or method might be included in the List if it fulfills at least two of the following criteria: enhances sports performance; represents a risk to the athlete's health; or violates the spirit of sports. This list, constantly updated to reflect new developments in the pharmaceutical industry as well as doping trends, enumerates the drug types and methods prohibited in and out of competition. Among the substances included are steroidal and peptide hormones and their modulators, stimulants, glucocorticosteroids, beta2-agonists, diuretics and masking agents, narcotics, and cannabinoids. Blood doping, tampering, infusions, and gene doping are examples of prohibited methods indicated on the List. From all these, hormones constitute by far the highest number of adverse analytical findings reported by antidoping laboratories. Although to date most are due to anabolic steroids, the advent of molecular biology techniques has made recombinant peptide hormones readily available. These substances are gradually changing the landscape of doping trends. Peptide hormones like erythropoietin (EPO), human growth hormone (hGH), insulin, and insulin-like growth factor I (IGF-I) are presumed to be widely abused for performance enhancement. Furthermore, as there is a paucity of techniques suitable for their detection, peptide hormones are all the more attractive to dishonest athletes. This article will overview the use of hormones as doping substances in sports, focusing mainly on peptide hormones as they represent a pressing challenge to the current fight against doping. Hormones and hormones modulators being developed by the pharmaceutical industry, which could emerge as new doping substances, are also discussed. 2008, Asian

  15. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice

    DEFF Research Database (Denmark)

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F

    2006-01-01

    Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like pepti...

  16. The adipokinetic hormone receptor modulates sexual behavior, pheromone perception and pheromone production in a sex-specific and starvation-dependent manner in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Sebastien eLebreton

    2016-01-01

    Full Text Available Food availability and nutritional status shape the reproductive activity of many animals. In rodents, hormones such as gonadotropin-releasing hormone (GnRH, restore energy homeostasis not only through regulating e.g. caloric intake and energy housekeeping, but also through modulating sex drive. We investigated whether the insect homologue of the GnRH receptor, the adipokinetic hormone receptor (AKHR modulates sexual behavior of the fruit fly Drosophila melanogaster depending on nutritional status. We found that AKHR regulates male, but not female sexual behavior in a starvation-dependent manner. Males lacking AKHR showed a severe decrease in their courtship activity when starved, as well as an increase in mating duration when fed. AKHR expression is particularly strong in the subesophageal zone (SEZ, Ito et al. 2014. We found axonal projections from AKHR-expressing neurons to higher brain centers including specific glomeruli in the antennal lobe. Among the glomeruli that received projections were those dedicated to detecting the male specific pheromone cis-vaccenyl acetate (cVA. Accordingly, responses to cVA were dependent on the nutritional status of flies. AKHR was also involved in the regulation of the production of cuticular pheromones, 7,11-heptacosadiene and 7-tricosene. This effect was observed only in females and depended on their feeding state. AKHR has therefore a dual role on both pheromone perception and production. For the first time our study shows an effect of AKHR on insect sexual behavior and physiology. Our results support the hypothesis of a conserved role of the GnRH/AKH pathway on a nutritional state-dependent regulation of reproduction in both vertebrates and invertebrates.

  17. Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems

    International Nuclear Information System (INIS)

    Audhya, T.; Manzione, M.M.; Nakane, T.; Kanie, N.; Passarelli, J.; Russo, M.; Hollander, C.S.

    1985-01-01

    Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH 2 ] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. The antibody to hpGRF(1-44)NH 2 is directed against the COOH-terminal region of the molecule, as shown by its cross reactivity with various hpGRF analogues. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125 I-labeled tracer. There was no cross reactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat

  18. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  19. The Role of Pregnancy, Perinatal Factors, and Hormones in Maternal Cancer Risk

    DEFF Research Database (Denmark)

    Troisi, Rebecca; Bjørge, Tone; Gissler, Mika

    2018-01-01

    differ by malignancy. Linking health-registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal etiology...

  20. Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

    Science.gov (United States)

    Schmitt-Ney, M; Happ, B; Hofer, P; Hynes, N E; Groner, B

    1992-12-01

    The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as

  1. Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling

    DEFF Research Database (Denmark)

    Argetsinger, L S; Norstedt, G; Billestrup, Nils

    1996-01-01

    In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is tyrosyl-phosphorylated following stimulation of 3T3-F442A fibroblasts with growth hormone (GH), leukemia inhibitory factor and interferon-gamma. In response to GH and leukemia inhibitory factor, IRS-2 is immediately...... for GH is further demonstrated by the finding that GH stimulates association of IRS-2 with the 85-kDa regulatory subunit of phosphatidylinositol 3'-kinase and with the protein-tyrosine phosphatase SHP2. These results are consistent with the possibility that IRS-2 is a downstream signaling partner...

  2. Anti-Müllerian hormone levels in salpingectomized compared with nonsalpingectomized women with tubal factor infertility and women with unexplained infertility

    DEFF Research Database (Denmark)

    Grynnerup, Anna Garcia-Alix Haugen; Lindhard, Anette; Sørensen, Steen

    2013-01-01

    To investigate the consequence of salpingectomy on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels before in vitro fertilization (IVF) treatment in salpingectomized women compared with nonsalpingectomized women with tubal factor infertility, women with unexplained infertility and...

  3. Role of hormonal factor in development of primary and secondary tumorous process in the brain

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Causes of the development onset of primary malignant cerebral neoplasms have not yet been determined. Not excluded is a possibility of unfavorable effect of the environment, genetic abnormalities, changes alterations in the hormonal background as well as metabolism, ionizing radiation: possible is also the role of viral infections and injuries. One of the main most severest complications of malignant tumors remain are metastatic lesions of the central nervous system whose proportion increases as with the patients’ longlivity. Cerebral metastases of malignant tumors are encountered more often than primary neoplasms of the central nervous system. The brain is not only a hormone-dependent organ the effect of sex hormones as early the embryonic state conditions normal development of the body as a whole and controls the sex related differentiation. It is known that neurons and glyocites like gonads and adrenal glands are able to produce steroid hormones. The enzymes responsible for the synthesis of neurosteroids were detected in the brain tissue in the embryonic period of the development. The human brain is not only a hormone-dependent organ effect influence of sex hormones as early as in the embrional state conditiones normal development of the body as a whole and controls sexual gender differentiation. It is known that neurons and glyocytes like gonads and adrenal glands are able to produce steroid hormones. Enzymes responsible for synthesis of neurosteroids were revealed in cerebral tissue both in during the embryonic period of the development and in adult condition. Besides there are have been obtained large amount of data on the presence in the cerebral cells of receptors to steroidal hormones. In various periods of life the influence effect exerted by steroids on nervous cells can change the morphofunctional state of the brain and manifests as altering myelinization, neuronal growth, and differentiation of nerve cells

  4. Maternal serum placental growth hormone, but not human placental lactogen or insulin growth factor-1, is positively associated with fetal growth in the first half of pregnancy

    DEFF Research Database (Denmark)

    Pedersen, N G; Juul, A; Christiansen, M

    2010-01-01

    To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy.......To investigate if maternal levels of human placental lactogen (hPL), placental growth hormone (PGH) and insulin-like growth factor-1 (IGF-1) are associated with growth rate of the biparietal diameter (BPD) in the first half of pregnancy....

  5. Cress oil modulates radiation-induced hormonal, histological, genetic disorders and sperm head abnormalities in albino rat

    International Nuclear Information System (INIS)

    Said, U.Z.; Azab, KH.SH.; Soliman, S.M.

    2005-01-01

    Watercress (Nasturtium officinale) is an aquatic perennial herb of mustard family. The plant is rich in glucosinolates, specially gluconasturtin, which can be hydrolyzed to 2- phenylethyl isothiocyanate (PEITC) and known to activate detoxification enzymes. Cress oil (0.1 ml/kg/day) was given to rats, receiving a standard diet, by gavage for 2 weeks before whole body gamma irradiation at 7 Gy (single dose) and treatment was continued one week after irradiation. The results obtained showed that cress oil treatment significantly diminished the radiation-induced alterations in levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin in serum and also blunted the increased levels of thiobarbituric acid reactive substances (TBARS) in serum and testes. Histopathological examination of testicular tissue showed that radiation exposure leads to atrophic testis with marked loss of germ cells, remaining tall pink Sertoli cells, peri tubular fibrosis and interstitial fibrosis. Cress oil treatments ameliorated the intensity of these changes where signs of partial recovery were observed in the histological configuration of leydig cells, seminiferous tubules, spermatocytes and in the structure of interstitial cells. Moreover, administration of cress oil significantly reduced the score of sperm head abnormalities and chromosomal aberration frequencies. It could be concluded that watercress may have a bio protective effect on radiation-induced oxidative stress where phytochemicals present in watercress could protect against hormone-dependent disease

  6. Regulatory cross-talks and cascades in rice hormone biosynthesis pathways contribute to stress signaling

    Directory of Open Access Journals (Sweden)

    Arindam Deb

    2016-08-01

    Full Text Available Crosstalk among different hormone signaling pathways play an important role in modulating plant response to both biotic and abiotic stress. Hormone activity is controlled by its bio-availability, which is again influenced by its biosynthesis. Thus independent hormone biosynthesis pathways must be regulated and co-ordinated to mount an integrated response. One of the possibilities is to use cis-regulatory elements to orchestrate expression of hormone biosynthesis genes. Analysis of CREs, associated with differentially expressed hormone biosynthesis related genes in rice leaf under Magnaporthe oryzae attack and drought stress enabled us to obtain insights about cross-talk among hormone biosynthesis pathways at the transcriptional level. We identified some master transcription regulators that co-ordinate different hormone biosynthesis pathways under stress. We found that Abscisic acid and Brassinosteroid regulate Cytokinin conjugation; conversely Brassinosteroid biosynthesis is affected by both Abscisic acid and Cytokinin. Jasmonic acid and Ethylene biosynthesis may be modulated by Abscisic acid through DREB transcription factors. Jasmonic acid or Salicylic acid biosynthesis pathways are co-regulated but they are unlikely to influence each other’s production directly. Thus multiple hormones may modulate hormone biosynthesis pathways through a complex regulatory network, where biosynthesis of one hormone is affected by several other contributing hormones.

  7. Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.

    Science.gov (United States)

    Donepudi, Ajay C; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L

    2016-04-01

    Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Effect of KiFAY on Performance, Insulin-like Growth Factor-1, and Thyroid Hormones in Broilers

    Directory of Open Access Journals (Sweden)

    Amit Kini

    2016-10-01

    Full Text Available A comparative study was performed to investigate the efficacy of KiFAY as a feed additive on performance parameters, thyroid, and pancreatic hormone levels in broilers. Ninety birds (Vencobb 400 were randomly divided into three groups viz., Control (no DL-methionine supplementation, Treatment1 (containing added DL-methionine and Treatment 2 (containing KiFAY and without DL-methionine supplementation. The performance parameters (weekly body weight, body weight gain, feed intake, and feed consumption ratio were recorded and calculated during the whole study of 4 weeks. Analyses of insulin and insulin-like growth factor (IGF 1, triiodothyronine (T3, thyroxine (T4 and thyroid stimulating hormone (TSH were performed at the end of the study. The results show that birds on supplementation of KiFAY performed significantly (p<0.001 better than other treatments. The weekly body weight, body weight gain, feed in-take and feed consumption ratio improved in KiFAY treated birds. The study found an increase in insulin and IGF1 levels (p<0.001 in KiFAY compared with the other treatments. Serum T3, T4, and TSH levels in the Treatment 2 were higher than other treatments (p<0.001. The KiFAY supplementation was able to improve performance with associated responses at a hormonal level in broilers.

  9. Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

    Science.gov (United States)

    Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

    2014-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

  10. Preliminary investigation of plasma levels of sex hormones and human growth factor(s, and P300 latency as correlates to cognitive decline as a function of gender

    Directory of Open Access Journals (Sweden)

    Kerner Mallory M

    2009-07-01

    Full Text Available Abstract Background Aging is marked by declines in levels of many sex hormones and growth factors, as well as in cognitive function. The P300 event-related potential has been established as a predictor of cognitive decline. We decided to determine if this measure, as well as 2 standard tests of memory and attention, may be correlated with serum levels of sex hormones and growth factors, and if there are any generalizations that could be made based on these parameters and the aging process. Findings In this large clinically based preliminary study several sex-stratified associations between hormone levels and cognition were observed, including (1 for males aged 30 to 49, both IGF-1 and IGFBP-3 significantly associated negatively with prolonged P300 latency; (2 for males aged 30 to 49, the spearman correlation between prolonged P300 latency and low free testosterone was significant; (3 for males aged 60 to 69, there was a significant negative correlation between P300 latency and DHEA levels; (4 for females aged 50 to 59 IGFBP-3 significantly associated negatively with prolonged P300 latency; (5 for females at all age periods, estrogen and progesterone were uncorrelated with P300 latency; and (6 for females aged 40 to 69, there was significant negative correlation between DHEA levels and P300 latency. Moreover there were no statistically significant correlations between any hormone and Wechsler Memory Scale-III (WMS-111. However, in females, there was a significant positive correlation between estrogen levels and the number of Attention Deficit Disorder (ADD complaints. Conclusion Given certain caveats including confounding factors involving psychiatric and other chronic diseases as well as medications, the results may still have important value. If these results could be confirmed in a more rigorously controlled investigation, it may have important value in the diagnosis, prevention and treatment of cognitive impairments and decline.

  11. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  12. Low calcium-phosphate intakes modulate the low-protein diet-related effect on peak bone mass acquisition: a hormonal and bone strength determinants study in female growing rats.

    Science.gov (United States)

    Fournier, C; Rizzoli, R; Ammann, P

    2014-11-01

    Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal

  13. A controlled study on serum insulin-like growth factor-I and urinary excretion of growth hormone in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, S; Main, K; Danneskiold-Samsøe, B

    1995-01-01

    It has been hypothesized that secretory deficiencies of growth hormone may play a pathophysiological role in fibromyalgia (FM). Our objective was thus to evaluate the secretion of growth hormone in FM.......It has been hypothesized that secretory deficiencies of growth hormone may play a pathophysiological role in fibromyalgia (FM). Our objective was thus to evaluate the secretion of growth hormone in FM....

  14. Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

    Directory of Open Access Journals (Sweden)

    Junghwan Suh

    2013-12-01

    Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

  15. Reproductive immunology: a focus on the role of female sex hormones and other gender-related factors.

    Science.gov (United States)

    Peeva, Elena

    2011-02-01

    Reproductive immunology has attracted the attention of researchers interested in fertility and pregnancy as well as those interested in immunity and autoimmunity. Over the past couple of decades, a wealth of data on the immune-reproductive interactions has been generated. This issue of the Journal will examine several topics including the role of immune factors in the induction of anti-Ro antibody-mediated autoimmunity in neonates and the immunological effects of gender and sex hormones. The possible implications of the research reviewed here for the development of novel therapeutic approaches are also addressed.

  16. The role of circulating sex hormones in menstrual cycle dependent modulation of pain-related brain activation

    Science.gov (United States)

    Veldhuijzen, Dieuwke S.; Keaser, Michael L.; Traub, Deborah S.; Zhuo, Jiachen; Gullapalli, Rao P.; Greenspan, Joel D.

    2013-01-01

    Sex differences in pain sensitivity have been consistently found but the basis for these differences is incompletely understood. The present study assessed how pain-related neural processing varies across the menstrual cycle in normally cycling, healthy females, and whether menstrual cycle effects are based on fluctuating sex hormone levels. Fifteen subjects participated in four test sessions during their menstrual, mid-follicular, ovulatory, and midluteal phases. Brain activity was measured while nonpainful and painful stimuli were applied with a pressure algometer. Serum hormone levels confirmed that scans were performed at appropriate cycle phases in 14 subjects. No significant cycle phase differences were found for pain intensity or unpleasantness ratings of stimuli applied during fMRI scans. However, lower pressure pain thresholds were found for follicular compared to other phases. Pain-specific brain activation was found in several regions traditionally associated with pain processing, including the medial thalamus, anterior and mid-insula, mid-cingulate, primary and secondary somatosensory cortices, cerebellum, and frontal regions. The inferior parietal lobule, occipital gyrus, cerebellum and several frontal regions demonstrated interaction effects between stimulus level and cycle phase, indicating differential processing of pain-related responses across menstrual cycle phases. Correlational analyses indicated that cycle-related changes in pain sensitivity measures and brain activation were only partly explained by varying sex hormone levels. These results show that pain-related cerebral activation varies significantly across the menstrual cycle, even when perceived pain intensity and unpleasantness remain constant. The involved brain regions suggest that cognitive pain or more general bodily awareness systems are most susceptible to menstrual cycle effects. PMID:23528204

  17. Cellular organization of pre-mRNA splicing factors in several tissues. Changes in the uterus by hormone action.

    Science.gov (United States)

    George-Téllez, R; Segura-Valdez, M L; González-Santos, L; Jiménez-García, L F

    2002-05-01

    In the mammalian cell nucleus, splicing factors are distributed in nuclear domains known as speckles or splicing factor compartments (SFCs). In cultured cells, these domains are dynamic and reflect transcriptional and splicing activities. We used immunofluorescence and confocal microscopy to monitor whether splicing factors in differentiated cells display similar features. Speckled patterns are observed in rat hepatocytes, beta-cells, bronchial and intestine epithelia and also in three cell types of the uterus. Moreover, the number, distribution and sizes of the speckles vary among them. In addition, we studied variations in the circular form (shape) of speckles in uterine cells that are transcriptionally modified by a hormone action. During proestrus of the estral cycle, speckles are irregular in shape while in diestrus I they are circular. Experimentally, in castrated rats luminal epithelial cells show a pattern where speckles are dramatically rounded, but they recover their irregular shape rapidly after an injection of estradiol. The same results were observed in muscle and gland epithelial cells of the uterus. We concluded that different speckled patterns are present in various cells types in differentiated tissues and that these patterns change in the uterus depending upon the presence or absence of hormones such as estradiol.

  18. Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells.

    Science.gov (United States)

    Somjen, D; Knoll, E; Sharon, O; Many, A; Stern, N

    2015-04-01

    Estrogen receptors (ERα and ERβ), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERβ expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERβ, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD.

    Science.gov (United States)

    Fenchel, Daphna; Levkovitz, Yechiel; Vainer, Ella; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

    2015-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely linked with the ability to inhibit the other. Testosterone, a product of the HPG, has many beneficial effects beyond its functions as a sex hormone including anti-anxiety properties. In this study we examined the effect of stress exposure on gonadal hormones, and their efficacy in modulating anxiety-like response in an animal model of PTSD. Male rats were exposed to predator scent stress, followed by analysis of brain expression of androgen receptor (AR) receptor and estrogen receptor α (ERα). The behavioral effects of immediate treatment with testosterone, testosterone receptor antagonist (flutamide) or vehicle were evaluated using the elevated plus-maze, acoustic startle response and trauma-cue response. Levels of circulating corticosterone and testosterone were also measured after treatment. The behavioral effects of delayed testosterone treatment were explored in the same manner. We report that animals whose behavior was extremely disrupted (EBR) selectively displayed significant down-regulation of AR and ERα in the hippocampus. Immediate treatment with flutamide or delayed treatment with testosterone significantly increased prevalence rates of minimal behavioral response (MBR) and decreased prevalence of EBR with favorable behavioral results. Testosterone levels were higher in control un-exposed animals, while corticosterone was higher in control exposed animals. This study suggests that gonadal steroid hormones are involved in the neurobiological response to predator scent stress and thus warrant further study as a potential therapeutic avenue for the treatment of anxiety-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  20. Insulin-like growth factor 1 and growth hormone in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Becker, Povl Ulrik

    1992-01-01

    , and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease and may be due to a disturbed regulation. Alterations in liver IGF receptors in patients with chronic liver disease still require investigation as they may be important for the liver...... mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment, and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feedback system acting on hepatic, pituitary...

  1. Ascorbate oxidase-dependent changes in the redox state of the apoplast modulate gene transcript accumulation leading to modified hormone signaling and orchestration of defense processes in tobacco.

    Science.gov (United States)

    Pignocchi, Cristina; Kiddle, Guy; Hernández, Iker; Foster, Simon J; Asensi, Amparo; Taybi, Tahar; Barnes, Jeremy; Foyer, Christine H

    2006-06-01

    The role of the redox state of the apoplast in hormone responses, signaling cascades, and gene expression was studied in transgenic tobacco (Nicotiana tabacum) plants with modified cell wall-localized ascorbate oxidase (AO). High AO activity specifically decreased the ascorbic acid (AA) content of the apoplast and altered plant growth responses triggered by hormones. Auxin stimulated shoot growth only when the apoplastic AA pool was reduced in wild-type or AO antisense lines. Oxidation of apoplastic AA in AO sense lines was associated with loss of the auxin response, higher mitogen-activated protein kinase activities, and susceptibility to a virulent strain of the pathogen Pseudomonas syringae. The total leaf glutathione pool, the ratio of reduced glutathione to glutathione disulfide, and glutathione reductase activities were similar in the leaves of all lines. However, AO sense leaves exhibited significantly lower dehydroascorbate reductase and ascorbate peroxidase activities than wild-type and antisense leaves. The abundance of mRNAs encoding antioxidant enzymes was similar in all lines. However, the day/night rhythms in the abundance of transcripts encoding the three catalase isoforms were changed in response to the AA content of the apoplast. Other transcripts influenced by AO included photorespiratory genes and a plasma membrane Ca(2+) channel-associated gene. We conclude that the redox state of the apoplast modulates plant growth and defense responses by regulating signal transduction cascades and gene expression patterns. Hence, AO activity, which modulates the redox state of the apoplastic AA pool, strongly influences the responses of plant cells to external and internal stimuli.

  2. Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency.

    Science.gov (United States)

    Hirohata, Toshio; Saito, Nobuhito; Takano, Koji; Yamada, So; Son, Jae-Hyun; Yamada, Shoko M; Nakaguchi, Hiroshi; Hoya, Katsumi; Murakami, Mineko; Mizutani, Akiko; Okinaga, Hiroko; Matsuno, Akira

    2013-01-01

    Adult growth hormone (GH) deficiency (AGHD) in Japan is diagnosed based on peak GH concentrations during GH provocative tests such as GHRP-2 stimulation test. In this study, we aimed to evaluate the ability of serum insulin-like growth factor-1 (sIGF-1) and urinary GH (uGH) at the time of awakening to diagnose AGHD. Fifty-nine patients with pituitary disease (32 men and 27 women; age 20-85 y (57.5 ± 15.5, mean ± SD) underwent GHRP-2 stimulation and sIGF-1 testing. Thirty-six and 23 patients were diagnosed with and without severe AGHD, respectively based on a peak GH response of standard deviation score (IGF-1 SDS) based on age and sex. We determined whether uGH levels in urine samples from 42 of the 59 patients at awakening were above or below the sensitivity limit. We evaluated IGF-1 SDS and uGH levels in a control group of 15 healthy volunteers. Values for IGF-1 SDS were significantly lower in patients with, than without (-2.07 ± 1.77 vs.-0.03 ± 0.92, mean ± SD; p -1.4. IGF-1 SDS discriminated AGHD more effectively in patients aged ≤60 years. The χ2 test revealed a statistical relationship between uGH and AGHD (test statistic: 7.0104 ≥ χ2 (1; 0.01) = 6.6349). When IGF-1 SDS is < -1.4 or uGH is below the sensitivity limit, AGHD can be detected with high sensitivity.

  3. Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

    Science.gov (United States)

    Davis, J R; Sheppard, M C; Shakespear, R A; Lynch, S S; Clayton, R N

    1986-02-01

    It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Change and significance of serum inflammatory factors, NSE, S100 protein and stress hormone levels in patients with craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Rui-Feng Liu

    2017-09-01

    Full Text Available Objective: To investigate the change and significance of serum inflammatory factors, neuron specific enolase (NSE, S100 protein and stress hormone levels in patients with brain diseases. Methods: A total of 115 patients with craniocerebral injury were selected as the observation group, according to the Glasgow Coma Scale (GCS, they were divided into light-sized group (n=38, middle-sized group (n=40 and severe-sized group (n=37, at the same time the other 120 healthy subjects were selected as the control group. The levels of serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α and procalcitonin (PCT], neuron specific enolase (NSE, S100 protein and the stress hormone cortisol [(COR, adrenocorticotropic hormone (ACTH, β-endorphin (β-EP] of both groups were compared. Results: The levels of TNF-α, PCT, NSE, S100, COR, ACTH and β-EP in the observation group were (145.73±19.24 ng/L, (2.41±0.64 ng/mL, (38.11±12.28 ng/mL, (0.87±0.32 μg/L, (818.87±121.14 nmol/L, (107.38±13.94 ng/L, (126.74±39.04 ng/mL, which were significantly higher than control group, the difference was statistically significant; Comparison of indexes among the observation group, NF-α, PCT, NSE, S100, COR, ACTH and β-EP levels in the middle-sized group and severe-sized group were significantly higher than those in the light-sized group, and the levels in the severe-sized group were significantly higher than those of the middle-sized group, the difference was statistically significant. Conclusion: The levels of Serum inflammatory factors, NSE, S100 protein and stress hormone were significantly increased in patients with craniocerebral injury, the level was related to the degree of traumatic brain injury, which could be used as an important indicator to assess the severity of the disease.

  5. Space Vector Modulation for an Indirect Matrix Converter with Improved Input Power Factor

    Directory of Open Access Journals (Sweden)

    Nguyen Dinh Tuyen

    2017-04-01

    Full Text Available Pulse width modulation strategies have been developed for indirect matrix converters (IMCs in order to improve their performance. In indirect matrix converters, the LC input filter is used to remove input current harmonics and electromagnetic interference problems. Unfortunately, due to the existence of the input filter, the input power factor is diminished, especially during operation at low voltage outputs. In this paper, a new space vector modulation (SVM is proposed to compensate for the input power factor of the indirect matrix converter. Both computer simulation and experimental studies through hardware implementation were performed to verify the effectiveness of the proposed modulation strategy.

  6. Modulation of intestinal and liver fatty acid-binding proteins in Caco-2 cells by lipids, hormones and cytokines.

    NARCIS (Netherlands)

    Dube, N.; Delvin, E.; Yotov, W.; Garofalo, C.; Bendayan, M.; Veerkamp, J.H.; Levy, E.

    2001-01-01

    Intestinal and liver fatty acid binding proteins (I- and L-FABP) are thought to play a role in enterocyte fatty acid (FA) trafficking. Their modulation by cell differentiation and various potential effectors was investigated in the human Caco-2 cell line. With the acquisition of enterocytic

  7. Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT).

    Science.gov (United States)

    Mortensen, Anne Skjetne; Arukwe, Augustine

    2007-04-01

    Multiple biological effects of tributyltin (TBT) on juvenile salmon have been investigated. Fish were exposed for 7 days to waterborne TBT at nominal concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). Hepatic samples were analyzed for gene expression patterns in the hormonal and xenobiotic biotransformation pathways using validated real-time PCR method. Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced concentration-specific decrease of estrogen receptor-alpha (ERalpha), vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal pathway. In the xenobiotic biotransformation pathway, TBT produced apparent increase and decrease at respective low and high concentration, on aryl hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT concentration-dependent decrease. The AhRbeta, CYP3A and uridine diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 protein levels confirmed the TBT effects observed at the transcriptional levels. The effect of TBT on the biotransformation enzyme gene expressions partially co-related but did not directly parallel enzyme activity levels for EROD, BROD, MROD and PROD. In general, these findings confirm previous reports on the endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at the transcriptional level that transcends to protein and enzymatic levels. The induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on CYP3A is proposed to

  8. Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test

    DEFF Research Database (Denmark)

    Montelius, Caroline; Szwiec, Katarzyna; Kardas, Marek

    2014-01-01

    BACKGROUND & AIMS: Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose...... metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet. METHODS: Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1 g/kg d-glucose) was performed. The experiment was designed as a cross-over study......, either with or without addition of 0.5 g/kg body weight of thylakoid powder. RESULTS: The supplementation of thylakoids to the oral glucose tolerance test resulted in decreased blood glucose concentrations during the first hour, increased plasma cholecystokinin concentrations during the first two hours...

  9. Hormonal therapy followed by chemotherapy or the reverse sequence as first-line treatment of hormone-responsive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients: results of an observational study.

    Science.gov (United States)

    Bighin, Claudia; Dozin, Beatrice; Poggio, Francesca; Ceppi, Marcello; Bruzzi, Paolo; D'Alonzo, Alessia; Levaggi, Alessia; Giraudi, Sara; Lambertini, Matteo; Miglietta, Loredana; Vaglica, Marina; Fontana, Vincenzo; Iacono, Giuseppina; Pronzato, Paolo; Del Mastro, Lucia

    2017-07-04

    Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

  10. Insulin-like growth factor-1 is a negative modulator of glucagon secretion

    OpenAIRE

    Mancuso, Elettra; Mannino, Gaia C.; Fatta, Concetta Di; Fuoco, Anastasia; Spiga, Rosangela; Andreozzi, Francesco; Sesti, Giorgio

    2017-01-01

    Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic ?-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of ?-cells glucagon secretion...

  11. Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Ravneet K. Boparai

    2015-01-01

    Full Text Available Fibroblast growth factor 21 (FGF21 modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly at the transcriptional level, we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21.

  12. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

    Directory of Open Access Journals (Sweden)

    Saenger Paul

    2012-05-01

    Full Text Available Abstract The term small for gestational age (SGA refers to infants whose birth weights and/or lengths are at least two standard deviation (SD units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH/insulin-like growth factor (IGF-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR polymorphism. Uniparental disomy (UPD and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  13. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

    Science.gov (United States)

    Nakagawa, S; Pawelek, P; Grinnell, F

    1989-06-01

    To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

  14. Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors

    Science.gov (United States)

    Mullington, Janet M.

    1999-01-01

    from this larger study: a 4.2 hour per night condition, and a 8.2 hour per night condition. During space flight, muscle mass and bone density are reduced, apparently due to loss of GH and IGF-I, associated with microgravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with the "Muscle Alterations and Atrophy Team ", we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the prediction that it will be reduced by chronic sleep restriction. In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood and until recently have gone largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. Moreover, in space flight, the possibility of compromised immune function or of the reactivation of latent viruses are serious potential hazards for the success of long term missions. Confined living conditions, reduced sleep, altered diet and stress are all factors that may compromise immune function, thereby increasing the risks of developing and transmitting disease. Medical complications, which would not pose serious problems on earth, may be disastrous if they emerged in space.

  15. A controlled study on serum insulin-like growth factor-I and urinary excretion of growth hormone in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, S; Main, K; Danneskiold-Samsøe, B

    1995-01-01

    OBJECTIVE. It has been hypothesized that secretory deficiencies of growth hormone may play a pathophysiological role in fibromyalgia (FM). Our objective was thus to evaluate the secretion of growth hormone in FM. METHODS. The 24-h urinary growth hormone excretion and serum levels of insulin...

  16. Energy regulation in context: Free-living female arctic ground squirrels modulate the relationship between thyroid hormones and activity among life history stages.

    Science.gov (United States)

    Wilsterman, Kathryn; Buck, C Loren; Barnes, Brian M; Williams, Cory T

    2015-09-01

    Thyroid hormones (THs), key regulators of lipid and carbohydrate metabolism, are likely modulators of energy allocation within and among animal life history stages. Despite their role in modulating metabolism, few studies have investigated whether THs vary among life history stages in free-living animals or if they exhibit stage-specific relationships to total energy expenditure and activity levels. We measured plasma total triiodothyronine (tT3) and thyroxine (tT4) at four, discrete life history stages of female arctic ground squirrels from two different populations in northern Alaska to test whether plasma THs correlate with life history stage-specific changes in metabolic rate and energy demand. We also tested whether THs explained individual variation in aboveground activity levels within life history stages. T3 peaked during lactation and was lowest during pre-hibernation fattening, consistent with known changes in basal metabolism and core body temperature. In contrast, T4 was elevated shortly after terminating hibernation but remained low and stable across other life-history stages in the active season. THs were consistently higher in the population that spent more time above-ground but the relationship between THs and activity varied among life history stages. T3 was positively correlated with activity only during lactation (r(2)=0.50) whereas T4 was positively correlated with activity immediately following lactation (r(2)=0.48) and during fattening (r(2)=0.53). Our results support the hypothesis that THs are an important modulator of basal metabolism but also suggest that the relationship between THs and activity varies among life history stages. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Identification and Expression Profiling of the Auxin Response Factors in Capsicum annuum L. under Abiotic Stress and Hormone Treatments

    Directory of Open Access Journals (Sweden)

    Chenliang Yu

    2017-12-01

    Full Text Available Auxin response factors (ARFs play important roles in regulating plant growth and development and response to environmental stress. An exhaustive analysis of the CaARF family was performed using the latest publicly available genome for pepper (Capsicum annuum L.. In total, 22 non-redundant CaARF gene family members in six classes were analyzed, including chromosome locations, gene structures, conserved motifs of proteins, phylogenetic relationships and Subcellular localization. Phylogenetic analysis of the ARFs from pepper (Capsicum annuum L., tomato (Solanum lycopersicum L., Arabidopsis and rice (Oryza sativa L. revealed both similarity and divergence between the four ARF families, and aided in predicting biological functions of the CaARFs. Furthermore, expression profiling of CaARFs was obtained in various organs and tissues using quantitative real-time RT-PCR (qRT-PCR. Expression analysis of these genes was also conducted with various hormones and abiotic treatments using qRT-PCR. Most CaARF genes were regulated by exogenous hormone treatments at the transcriptional level, and many CaARF genes were altered by abiotic stress. Systematic analysis of CaARF genes is imperative to elucidate the roles of CaARF family members in mediating auxin signaling in the adaptation of pepper to a challenging environment.

  18. Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

    Science.gov (United States)

    Laron, Zvi

    2005-02-01

    Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.

  19. Changes of serum insulin-like growth factor-1 and growth hormone levels in patients with Graves' disease

    International Nuclear Information System (INIS)

    Jin Yueling; Xie Kejian; Xia Yuxiang; Pan Furong

    2003-01-01

    Objective: To investigate the changes of serum insulin-like growth factor-1(IGF-1) and growth hormone (GH) levels in patients with Graves' disease (GD). Methods: The serum IGF-1 and GH levels were determined with RIA in 42 cases of GD, 20 cases of GD patients after therapy (in euthyroid state) and 30 normal controls. Results: The level of serum IGF-1 (170.8±44.4 ng/ml) and GH (2.80±1.18 ng/ml) were significantly higher in GD patients than those in controls [IGF-1 (90.5±30.5 ng/ml), GH(1.58±1.20 ng/ml)] (p<0.01, p<0.05). IGF-1 levels were positively correlated to FT4 levels (r=0.58, p<0.01). The levels of serum IGF-1 (110.4±33.2 ng/ml) and GH (1.71±1.36 ng/ml) after treatment were significantly lower than those before treatment (p<0.01, p<0.05). Conclusion: The levels of serum IGF-1 and GH were markedly increase in GD patients and might be influenced by changes of thyroid hormone levels

  20. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    Science.gov (United States)

    Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina

    2017-04-01

    Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P controls and was associated with significantly reduced plasma levels of mouse GH ( P controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.

  1. Analytical Investigation on the Power Factor of a Flux-Modulated Permanent-Magnet Synchronous Machine

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Liu, Xiao; Liu, Jinglin

    2015-01-01

    Flux-modulated permanent-magnet synchronous machine (FM-PMSM) is characterized as a high-torque direct-drive electrical machine, but may suffer from the low power factor. This paper aims to investigate the issue of the low power factor in theory and explore the possibilities for improvement...

  2. PI3K/Akt-independent NOS/HO activation accounts for the facilitatory effect of nicotine on acetylcholine renal vasodilations: modulation by ovarian hormones.

    Directory of Open Access Journals (Sweden)

    Eman Y Gohar

    Full Text Available We investigated the effect of chronic nicotine on cholinergically-mediated renal vasodilations in female rats and its modulation by the nitric oxide synthase (NOS/heme oxygenase (HO pathways. Dose-vasodilatory response curves of acetylcholine (0.01-2.43 nmol were established in isolated phenylephrine-preconstricted perfused kidneys obtained from rats treated with or without nicotine (0.5-4.0 mg/kg/day, 2 weeks. Acetylcholine vasodilations were potentiated by low nicotine doses (0.5 and 1 mg/kg/day in contrast to no effect for higher doses (2 and 4 mg/kg/day. The facilitatory effect of nicotine was acetylcholine specific because it was not observed with other vasodilators such as 5'-N-ethylcarboxamidoadenosine (NECA, adenosine receptor agonist or papaverine. Increases in NOS and HO-1 activities appear to mediate the nicotine-evoked enhancement of acetylcholine vasodilation because the latter was compromised after pharmacologic inhibition of NOS (L-NAME or HO-1 (zinc protoporphyrin, ZnPP. The renal protein expression of phosphorylated Akt was not affected by nicotine. We also show that the presence of the two ovarian hormones is necessary for the nicotine augmentation of acetylcholine vasodilations to manifest because nicotine facilitation was lost in kidneys of ovariectomized (OVX and restored after combined, but not individual, supplementation with medroxyprogesterone acetate (MPA and estrogen (E2. Together, the data suggests that chronic nicotine potentiates acetylcholine renal vasodilation in female rats via, at least partly, Akt-independent HO-1 upregulation. The facilitatory effect of nicotine is dose dependent and requires the presence of the two ovarian hormones.

  3. Factors influencing growth hormone levels of Bali cattle in Bali, Nusa Penida, and Sumbawa Islands, Indonesia.

    Science.gov (United States)

    Suwiti, N K; Besung, I N K; Mahardika, G N

    2017-10-01

    Bali cattle ( Bos javanicus ) are an Indonesian's native cattle breed that distributed in Asia to Australia. The scientific literature on these cattle is scarce. The growth hormone (GH) of Bali cattle is investigated from three separated islands, namely, Bali, Nusa Penida, and Sumbawa. Forty plasma samples were collected from each island, and the GH was measured using a commercial enzyme-linked immunosorbent assay kit. The data were analyzed based on the origin, sex, and cattle raising practices. We found that the GH level (bovine GH [BGH]) of animal kept in stall 1.72±0.70 µg/ml was higher than free-grazing animal 1.27±0.81 µg/ml. The GH level was lower in female (1.22±0.62 µg/ml) compared to male animals (1.77±0.83 µg/ml). We conclude that the level of BGH in Bali cattle was low and statistically equal from all origins. The different level was related to sex and management practices. Further validation is needed through observing the growth rate following BGH administration and discovering the inbreeding coefficient of the animal in Indonesia.

  4. The Effects of 17 Weeks of Ballet Training on the Autonomic Modulation, Hormonal and General Biochemical Profile of Female Adolescents

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    da Silva Carla Cristiane

    2015-09-01

    Full Text Available This study aimed to examine the alterations in physiological and biochemical markers, after 17 weeks of ballet training in high level ballet dancers. Twenty four female ballet dancers from 12 to 15 years old took part in the study. The study followed 17 weeks of ballet training and analyzed changes in body composition, the autonomic nervous system and biochemical variables before and after (post training. The internal training load was obtained using the session rating of perceived exertion (session-RPE method, calculated as the mean weekly session-RPE, monotony and strain. After 17 weeks of training there were significant increases in body mass, height, lean body mass, total protein, urea, hemoglobin concentration, testosterone and thyroxine. During this period, decreases in relative body fat, uric acid, red blood cells, C-reactive protein, and ferritin were also found. After the training period, the autonomic modulation demonstrated significant positive alterations, such as increases in parasympathetic related indices. Based on the results obtained we concluded that ballet training led to improvements in body composition and autonomic modulation. In general hematological and biochemical variables demonstrated that the training did not have adverse effects on the health state of the adolescents.

  5. Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

    Science.gov (United States)

    Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2007-01-01

    Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

  6. The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

    Science.gov (United States)

    Arnold, Edith; Thebault, Stéphanie; Baeza-Cruz, German; Arredondo Zamarripa, David; Adán, Norma; Quintanar-Stéphano, Andrés; Condés-Lara, Miguel; Rojas-Piloni, Gerardo; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2014-01-29

    Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.

  7. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats

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    Chuin Hau Teo

    2017-09-01

    Full Text Available Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH. The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin—which has been shown to be affected by circadian proteins such as Bmal1—in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  8. Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats.

    Science.gov (United States)

    Teo, Chuin Hau; Soga, Tomoko; Parhar, Ishwar S

    2017-01-01

    Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH) acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH). The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH) in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin-which has been shown to be affected by circadian proteins such as Bmal1-in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

  9. Modulation of catechol estrogen synthesis by rat liver microsomes: effects of treatment with growth hormone or testosterone

    International Nuclear Information System (INIS)

    Quail, J.A.; Jellinck, P.H.

    1987-01-01

    The ability of GH from various mammalian species, administered to normal mature male rats by constant infusion, to decrease the hepatic 2-hydroxylation of estradiol (E2) to female levels, as measured by the release of 3 H 2 O from [2-3H]E2, was determined. Rat and human GH (hGH) showed the highest activity while ovine GH was inactive. PRL (0.6 IU/h X kg) administered together with hGH (0.02 IU/h X kg) did not antagonize the feminizing action of GH. Infusion of hGH into male rats decreased the affinity of estradiol 2-hydroxylase for its steroid substrate and altered the linear Lineweaver-Burk plot towards a nonlinear hyperbolic plot characteristic of the female. The apparent Michaelis-Menten constant (Km) for the reaction was 1.69 microM for males and 2.75 microM for testosterone-treated ovariectomized females. An equal mixture of liver microsomes from male and female rats gave kinetic values similar to those observed with males alone. Neonatal imprinting with androgen did not alter the magnitude of the response of female rats to treatment with testosterone and/or GH at maturity and the androgen effect could only be shown in ovariectomized animals. The results with rats of different endocrine status were corroborated by the kinetic data and by the pattern of metabolites obtained with [4- 14 C]E2 when examined by TLC and autoradiography. The hormonal control of estradiol 2-hydroxylase, the key enzyme in catechol estrogen formation, and the contribution of sex-specific multiple forms of the enzyme to this reaction are discussed

  10. Modulation of hemopoiesis by novel stromal cell factors

    International Nuclear Information System (INIS)

    Zipori, D.

    1988-01-01

    The microenvironment of the bone marrow in mammals is a crucial site for the maintenance of a pluripotent hemopoietic stem cell pool. Our previous studies and present findings support the notion that both this function and the fine architecture of hemopoietic organs, i.e., the spatial arrangement of blood cells within the tissue, may be directed by stromal cells. Despite the ability of cloned stromal cells to support prolonged hempoiesis and maintenance in vitro of stem cells with high radioprotective ability, they are a poor source of colony stimulating factor-1 (CSF-1) and do not secrete the other species of CSF. Furthermore, cultured stromal cells antagonize the activity of CSF. It is proposed that stromal cell factors distinct from known CSFs, regulate stem cell renewal. An additional phenomenon that is mediated by stromal cells and can not be attributed to CSF, is their ability to specifically inhibit the accumulation of cells of particular lineage and stage of differentiation. A glycoprotein that inhibits the growth of plasmacytomas but not a variety of other cell types was isolated from one type of cloned stromal cells. Such specific inhibitors may account for the control of cell localization in the hemopoietic system

  11. Cultural and biological factors modulate spatial biases over development.

    Science.gov (United States)

    Girelli, Luisa; Marinelli, Chiara Valeria; Grossi, Giuseppe; Arduino, Lisa S

    2017-11-01

    Increasing evidence supports the contribution of both biological and cultural factors to visuospatial processing. The present study adds to the literature by exploring the interplay of perceptual and linguistic mechanisms in determining visuospatial asymmetries in adults (Experiment 1) and children (Experiment 2). In particular, pre-schoolers (3 and 5 year-olds), school-aged children (8 year-old), and adult participants were required to bisect different types of stimuli, that is, lines, words, and figure strings. In accordance with the literature, results yielded a leftward bias for lines and words and a rightward bias for figure strings, in adult participants. More critically, different biases were found for lines, words, and figure strings in children as a function of age, reflecting the impact of both cultural and biological factors on the processing of different visuospatial materials. Specifically, an adult-like pattern of results emerged only in the older group of children (8 year-old), but not in pre-schoolers. Results are discussed in terms of literacy, reading habits exposure, and biological maturation.

  12. Modulation of the Genome and Epigenome of Individuals Susceptible to Autism by Environmental Risk Factors

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    Costas Koufaris

    2015-04-01

    Full Text Available Diverse environmental factors have been implicated with the development of autism spectrum disorders (ASD. Genetic factors also underlie the differential vulnerability to environmental risk factors of susceptible individuals. Currently the way in which environmental risk factors interact with genetic factors to increase the incidence of ASD is not well understood. A greater understanding of the metabolic, cellular, and biochemical events involved in gene x environment interactions in ASD would have important implications for the prevention and possible treatment of the disorder. In this review we discuss various established and more alternative processes through which environmental factors implicated in ASD can modulate the genome and epigenome of genetically-susceptible individuals.

  13. Growth hormone-insulin-like growth factor-1 and inflammatory response to a single exercise bout in children and adolescents.

    Science.gov (United States)

    Nemet, Dan; Eliakim, Alon

    2010-01-01

    Physical activity plays an important role in tissue anabolism, growth and development, but the mechanisms that link patterns of exercise with tissue anabolism are not completely understood. The effectiveness of physical training depends on the training load and on the individual ability to tolerate it, and an imbalance between the two may lead to under or over-training. Therefore, many efforts have been made to find objective parameters to quantify the balance between training load and the athlete's tolerance. One of the unique features of exercise is that it leads to a simultaneous increase of antagonistic mediators. On the one hand, exercise stimulates anabolic components of the growth hormone (GH) → IGF-1 (insulin-like growth factor-1) axis. On the other hand, exercise elevates catabolic pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α). This emphasizes probably the importance of optimal adaptation to exercise in particularly during adolescence. The very fine balance between the anabolic and inflammatory/catabolic response to exercise will determine the effectiveness of exercise training and the health consequences of exercise. If the anabolic response is stronger, exercise will probably lead ultimately to increased muscle mass and improved fitness. A greater catabolic response, in particularly if persists for long duration, may lead to overtraining. Therefore, changes in the anabolic-catabolic hormonal balance and in circulating inflammatory cytokines can be used by adolescent athletes and/or their coaches to gauge the training intensity in individual and team sports. Copyright © 2010 S. Karger AG, Basel.

  14. Evaluation of insulin-like growth factor-1 and insulin like growth factor binding protein-3 in diagnosis of growth hormone deficiency in short-stature children

    International Nuclear Information System (INIS)

    Ali, A.; Hashim, R.; Khan, F.A.; Sattar, A.; Ijaz, A.; Manzoor, S.M.; Younas, M.

    2009-01-01

    Growth Hormone Deficiency (GHD) is conventionally diagnosed and confirmed by diminished peak Growth Hormone (GH) levels to provocative testing. Serum Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are under the influence of GH and reflect the spontaneous endogenous GH secretion. Owing to the absence of a circadian rhythm, it is possible to take individual measurements of IGF-1 and IGFBP-3 at any time of the day for evaluation of GH status instead of subjecting the individual to cumbersome provocative tests. Objectives of this study were to compare IGF-1 and IGFBP-3 assays with Exercise and L-Dopa stimulation tests in the diagnosis of growth hormone deficiency in short stature children using ITT as gold standard. Methods: This validation study was conducted at Department of Chemical Pathology and Endocrinology, AFIP, Rawalpindi, from November 2005 to October 2006. Fifty-two short stature children were included in the study. Basal samples for GH levels and simultaneous IGF-1 and IGFBP-3 measurements were obtained and afterwards all children were subjected to sequential exercise and LDopa stimulation tests. Insulin Tolerance Test (ITT) was performed one week later with all the necessary precautionary measures. On the basis of ITT results, children were divided into two groups, i.e., 31 growth hormone deficient and 21 Normal Variant Short Stature (NVSS). Results: The diagnostic value of exercise stimulation test remained highest with sensitivity 90.3%, specificity 76.0%, Positive Predictive Value (PPV) 84.84%, Negative Predictive Value (NPV) 84.2% and accuracy 84.6%. The conventional L-Dopa stimulation had sensitivity 96.7%, specificity 38.0%, PPV 69.7%, NPV 88.8 % and accuracy 73.0%. The serum IGF-1 and IGFBP-3 levels were positively correlated with post ITT peak GH levels (r= 0.527, r=0.464 respectively, both p<0.001). The diagnostic value of IGF-1 had sensitivity 83.87%, specificity 76.2%, PPV 83.87%, NPV 76.2% and

  15. Multiple endocrine neoplasia (MEN) - like syndrome and other hormonal factors of promotion and progression of thyroid gland cancer in males-liquidators of Chernobyl accident consequences

    International Nuclear Information System (INIS)

    Strukov, E.L.; Dryguina, L.B.; Nikiforova, I.D.

    1997-01-01

    The clinical and laboratory endocrinological screening performed in 1,000 males - liquidators of Chernobyl accident consequences revealed hormonal factors leading to node formation and having unfavourable influence on progression and promotion of thyroid gland cancer. The factors include syndrome of low thriiodothyronine, hyperprolactinemia, latent hypothyrosis and increased production of thyroglobulin. Peculiarities of hormonal status in liquidators allow us to suggest the presence of MEN-like syndrome among the liquidators population. Possible mechanisms of expression of RET oncogene in adults that may result in MEN- like syndrome have been discussed. (author)

  16. Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

    Science.gov (United States)

    Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

    2018-01-04

    Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus.

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    Yiu Chung Tse

    Full Text Available Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs, which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow-onset (>1 hour after termination of CORT exposure increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP and long-term depression (LTD within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation.

  18. Social factors modulate restraint stress induced hyperthermia in mice.

    Science.gov (United States)

    Watanabe, Shigeru

    2015-10-22

    Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Dlk1/FA1 Is a Novel Endocrine Regulator of Bone and Fat Mass and Its Serum Level Is Modulated By Growth Hormone

    DEFF Research Database (Denmark)

    Abdallah, B.M.; Ding, M.; Jensen, C.H.

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. FA1 (fetal antigen 1) is the soluble form of dlk1 (delta like 1), which is a member of the Notch-Delta family. We have previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1-mice) using the hydrodynamic-based gene transfer procedure (HGTP). We found that increased serum FA1 levels led to a significant reduction in total body weight......, fat mass and bone mass in a dose-dependent manner. Reduced bone mass in FA1-mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58% and 72% respectively. Since FA1 is co-localized with growth hormone (GH) in the pituitary gland, we explored the possible...

  20. Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A-like inhibitor of differentiation 1 (EID1

    Directory of Open Access Journals (Sweden)

    Diana Vargas

    2008-01-01

    Full Text Available Transcriptional activation (TA mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A associated 300 kDa binding protein (p300 and the cAMP response element binding protein (CREB binding protein (CBP, known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR mediated TA but the E1A-like inhibitor of differentiation 1 (EID1, an inhibitor of p300 histone acetyltransferase (HAT, is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.

  1. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    Science.gov (United States)

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  2. Luteinizing hormone-induced Akt phosphorylation and androgen production are modulated by MAP Kinase in bovine theca cells

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    Fukuda Shin

    2009-11-01

    Full Text Available Abstract Background Theca cells play an important role in controlling ovarian steroidogenesis by providing aromatizable androgens for granulosa cell estrogen biosynthesis. Although it is well established that the steroidogenic activity of theca cells is mainly regulated by LH, the intracellular signal transduction mechanisms that regulate thecal proliferation and/or steroidogenesis remain obscure. In this study, we examined whether and how LH controls the PI3K/Akt signaling pathway and androgen production in bovine theca cells. We also explored whether this LH-induced PI3K/Akt activation is modulated with other signaling pathways (i.e. PKA and MAPK. Methods Ovarian theca cells were isolated from bovine small antral follicles and were incubated with LH for various durations. Phospho-Akt and total-Akt content in the cultured theca cells were examined using Western blotting. Androstenedione levels in the spent media were determined using EIA. Semi-quantitative RT-PCR analyses were conducted to analyze the mRNA levels of CYP17A1 and StAR in the theca cells. To examine whether Akt activity is involved in theca cell androgen production, the PI3K inhibitors wortmannin and LY294002 were also added to the cells. Results Akt is constitutively expressed, but is gradually phosphorylated in cultured bovine theca cells through exposure to LH. LH significantly increased androstenedione production in bovine theca cells, whereas addition of the wortmannin and LY294002 significantly decreased LH-induced androstenedione production. LH significantly increased CYP17A1 mRNA level in theca cells, whereas addition of LY294002 significantly decreased LH-induced CYP17A1 expression. Neither LH nor PI3K inhibitors alter the mRNA levels of StAR in theca cells. Although H89 (a selective inhibitor of PKA does not affect LH-mediated changes in Akt, U0126 (a potent MEK inhibitor suppressed LH-induced Akt phosphorylation, CYP17A1 expression, and androgen production in theca

  3. Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A; Arnold, Robyn E

    2005-03-01

    Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.

  4. Intermittent hypoxia suppression of growth hormone and insulin-like growth factor-I in the neonatal rat liver.

    Science.gov (United States)

    Cai, Charles; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V; Xu, Jiliu; Beharry, Kay D

    2018-03-08

    Extremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis. Newborn rats were exposed to 2, 4, 6, 8, 10, or 12 hypoxic episodes (12% O 2 ) during hyperoxia (50% O 2 ) from P0-P7, P0-P14 (IH), or allowed to recover from P7-P21 or P14-P21 (IHR) in room air (RA). RA littermates at P7, P14, and P21 served as RA controls; and groups exposed to hyperoxia only (50% O 2 ) served as zero IH controls. Histopathology of the liver; hepatic levels of GH, GHBP, IGF-I, IGFBP-3, and leptin; and immunoreactivities of GH, GHR, IGF-I and IGF-IR were determined. Pathological findings of the liver, including cellular swelling, steatosis, necrosis and focal sinusoid congestion were seen in IH, and were particularly severe in the P7 animals. Hepatic GH levels were significantly suppressed in the IH groups exposed to 6-12 hypoxic episodes per day and were not normalized during IHR. Deficits in the GH levels were associated with reduced body length and increase body weight during IHR suggesting increased adiposity and catchup fat. Catchup fat was also associated with elevations in GHBP, IGF-I, leptin. IH significantly impairs hepatic GH/IGF-1 signaling during the first few weeks of life, which is likely responsible for hepatic GH resistance, increased body fat, and hepatic steatosis. These hormonal perturbations may contribute to long-term organ and body growth impairment, and metabolic dysfunction in preterm infants experiencing frequent IH and/or apneic episodes. Copyright © 2018

  5. Modulation of gene expression in small follicle porcine granulosa cells by human follicle stimulating hormone (hFSH)

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.O.; Ryan, R.J.; Woloschak, G.E.

    1986-03-01

    Small follicle (1-3 mm) porcine granulosa cells (SFPGF) were isolated by puncture, aspiration and cultured under standard conditions in DMEM, HEPES, BSA, MIX. At the start of culture, cells were stimulated with 100ng hFSH/ml. At various times afterwards total cellular RNA was prepared using guanidine-hydrochloride solubilization, phenol extraction and precipitation from 3M NaOAc, pH 6.0. RNA was 5'-end labelled with /sup 32/P in a kinase reaction and hybridized to an excess of clone-specific DNA immobilized on nitrocellulose filters using stringent hybridization and wash conditions. After autoradiography the RNA hybridized to the DNA blot filter were quantitated by microdensitometry. Hybridization to parent plasmid was negative. RNA derived from control cultures showed patterns of hybridization similar to those obtained from freshly obtained cells. Results of these experiments demonstrate hFSh induction of RNA specific for transferrin receptor, ..cap alpha..-interferon, H-ras, and K-ras. Increased RNA levels were apparent within 10 min of treatment and had declined by 180 min. Expression of actin, p53 and for RNAs declined by 10 min of hFSH addition but was enhanced by 160 min. Levels of ..beta..-interferon, myc, mos, abl and yb RNAs were not detectable under these conditions. These results demonstrate specific gene modulation in SFPGC cultured with hFSH.

  6. Social Modulation or Hormonal Causation? Linkages of Testosterone with Sexual Activity and Relationship Quality in a Nationally Representative Longitudinal Sample of Older Adults.

    Science.gov (United States)

    Das, Aniruddha; Sawin, Nicole

    2016-11-01

    This study used population-representative longitudinal data from the 2005-2006 and 2010-2011 waves of the National Social Life, Health and Aging Project-a probability sample of US adults aged 57-85 at baseline (N = 650 women and 620 men)-to examine the causal direction in linkages of endogenous testosterone (T) with sexual activity and relationship quality. For both genders, our autoregressive effects indicated a large amount of temporal stability, not just in individual-level attributes (T, masturbation) but also dyadic ones (partnered sex, relationship quality)-indicating that a need for more nuanced theories of relational processes. Cross-lagged results suggested gender-specific effects-generally more consistent with sexual or relational modulation of T than with hormonal causation. Specifically, men's findings indicated their T might be elevated by their sexual (masturbatory) activity but not vice versa, although androgen levels did lower men's subsequent relationship quality. Women's T, in contrast, was negatively influenced not just by their higher relationship quality but also by their more frequent partnered sex-perhaps reflecting a changing function of sexual activity in late life.

  7. Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle.

    Science.gov (United States)

    Becú-Villalobos, Damasia; García-Tornadú, Isabel; Shroeder, Guillermo; Salado, Eloy E; Gagliostro, Gerardo; Delavaud, Carole; Chilliard, Yves; Lacau-Mengido, Isabel M

    2007-07-01

    We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil such that the diets were isocaloric; 18 cows received the fat-substituted diet and 18 a control diet from day 20 before the expected calving date to day 75 postpartum. In experiment 3, calcium salts of fatty acids were added to the basal diet of 14 feedlot steers for 80 d; another 14 steers received a control diet. The basal plasma levels of leptin were higher in the cows than in the steers. Dietary fat supplementation did not affect the leptin levels in the lactating cows but lowered the levels in the feedlot steers despite greater energy intake and body fatness (body weight) in the steers receiving the supplement than in those receiving the control diet. The levels of insulin-like growth factor I and insulin were decreased with dietary fat supplementation in the lactating cows but were unaffected in the steers, suggesting that responses to fat ingestion depend on the physiological state of the animal, including age and sex. Finally, no effects of supplementary fat on the level of growth hormone were demonstrated in any of the models.

  8. Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone.

    Science.gov (United States)

    Emilov-Velev, K; Clemente-de-Arriba, C; Alobera-García, M Á; Moreno-Sansalvador, E M; Campo-Loarte, J

    2015-01-01

    Many substances (growth factors and hormones) have osteoinduction properties and when added to some osteoconduction biomaterial they accelerate bone neoformation properties. The materials included 15 New Zealand rabbits, calcium phosphate cement (Calcibon(®)), human growth hormone (GH), and plasma rich in platelets (PRP). Each animal was operated on in both proximal tibias and a critical size bone defect of 6mm of diameter was made. The animals were separated into the following study groups: Control (regeneration only by Calcibon®), PRP (regeneration by Calcibon® and PRP), GH (regeneration by Calcibon® and GH). All the animals were sacrificed at 28 days. An evaluation was made of the appearance of the proximal extreme of rabbit tibiae in all the animals, and to check the filling of the critical size defect. A histological assessment was made of the tissue response, the presence of new bone formation, and the appearance of the biomaterial. Morphometry was performed using the MIP 45 image analyser. ANOVA statistical analysis was performed using the Statgraphics software application. The macroscopic appearance of the critical defect was better in the PRP and the GH group than in the control group. Histologically greater new bone formation was found in the PRP and GH groups. No statistically significant differences were detected in the morphometric study between bone formation observed in the PRP group and the control group. Significant differences in increased bone formation were found in the GH group (p=0.03) compared to the other two groups. GH facilitates bone regeneration in critical defects filled with calcium phosphate cement in the time period studied in New Zealand rabbits. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  9. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  10. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  11. Hormone assay

    International Nuclear Information System (INIS)

    Eisentraut, A.M.

    1977-01-01

    An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

  12. Protein-Enriched Liquid Preloads Varying in Macronutrient Content Modulate Appetite and Appetite-Regulating Hormones in Healthy Adults.

    Science.gov (United States)

    Dougkas, Anestis; Östman, Elin

    2016-03-01

    Dietary protein is considered the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributable to the protein or to the concomitant manipulation of carbohydrates and fat. The aim was to examine the effect of consumption of preloads varying in macronutrient content on appetite, energy intake, and biomarkers of satiety. Using a randomized, within-subjects, 2-level factorial design, 36 adults [mean ± SD age: 27 ± 5 y; body mass index (in kg/m(2)): 24.3 ± 1.6) received a breakfast consisting of 1 of 7 isovolumetric (670 mL) and isoenergetic (2100 kJ) liquid preloads matched for energy density and sensory properties but with different macronutrient composition (levels: 9%, 24%, or 40% of energy from protein combined with a carbohydrate-to-fat ratio of 0.4, 2, or 3.6, respectively). Appetite ratings and blood samples were collected and assessed at baseline and every 30 and 60 min, respectively, until a lunch test meal, which participants consumed ad libitum, was served 3.5 h after breakfast. Prospective consumption was 12% lower after intake of the high-protein (40%)/3.6 carbohydrate:fat preload than after intake of the low-protein (9%)/0.4 carbohydrate:fat preload (P = 0.02) solely because of the increased protein, irrespective of the manipulation of the other macronutrients. Most appetite ratings tended to be suppressed (13%) with increasing protein content of the preloads (P appetite than did carbohydrates and fat. Modulating the nutritional profile of a meal by replacing fat with protein can influence appetite in healthy adults. This trial was registered at www.clinicaltrials.gov as NCT01849302. © 2016 American Society for Nutrition.

  13. The Forkhead Transcription Factor, Foxd1, Is Necessary for Pituitary Luteinizing Hormone Expression in Mice

    Science.gov (United States)

    Gumbel, Jason H.; Patterson, Elizabeth M.; Owusu, Sarah A.; Kabat, Brock E.; Jung, Deborah O.; Simmons, Jasmine; Hopkins, Torin; Ellsworth, Buffy S.

    2012-01-01

    The pituitary gland regulates numerous physiological functions including growth, reproduction, temperature and metabolic homeostasis, lactation, and response to stress. Pituitary organogenesis is dependent on signaling factors that are produced in and around the developing pituitary. The studies described in this report reveal that the forkhead transcription factor, Foxd1, is not expressed in the developing mouse pituitary gland, but rather in the mesenchyme surrounding the pituitary gland, which is an essential source of signaling factors that regulate pituitary organogenesis. Loss of Foxd1 causes a morphological defect in which the anterior lobe of the pituitary gland protrudes through the cartilage plate that is developing ventral to the pituitary at embryonic days (e)14.5, e16.5, and e18.5. The number of proliferating pituitary cells is increased at e14.5 and e16.5. Loss of Foxd1 also results in significantly decreased levels of Lhb expression at e18.5. This decrease in Lhb expression does not appear to be due to a change in the number of gonadotrope cells in the pituitary gland. Previous studies have shown that loss of the LIM homeodomain factor, Lhx3, which is activated by the FGF signaling pathway, results in loss of LH production. Although there is a difference in Lhb expression in Foxd1 null mice, the expression pattern of LHX3 is not altered in Foxd1 null mice. These studies suggest that Foxd1 is indirectly required for normal Lhb expression and cartilage formation. PMID:23284914

  14. Trefoil factors are expressed in human and rat endocrine pancreas: differential regulation by growth hormone

    DEFF Research Database (Denmark)

    Jackerott, Malene; Lee, Ying C; Møllgård, Kjeld

    2006-01-01

    Trefoil factors (TFFs) 1, 2, and 3 are expressed in mucosal epithelia. TFFs are particular abundant in the intestine in which they play a crucial role in maintenance and restitution of the epithelium. Because pancreas developmentally arises from the primitive foregut, we explored the expression o...

  15. Hormonal and reproductive factors are associated with chronic low back pain and chronic upper extremity pain in women - The MORGEN study

    NARCIS (Netherlands)

    Wijnhoven, H. A H; de Vet, Henrica C W; Smit, Henriëtte A.; Picavet, H. Susan J

    STUDY DESIGN. Cross-sectional study of 11,428 women aged 20-59 years who were included in a postal questionnaire survey in the Dutch general population. OBJECTIVE. To examine how hormonal and reproductive factors are associated with chronic low back pain (LBP) and chronic upper extremity pain (UEP)

  16. Hormonal and reproductive factors are associated with chronic low back pain and chronic upper extremity pain in women--the MORGEN study.

    NARCIS (Netherlands)

    Wijnhoven, Hanneke A H; Vet, Henrica C W de; Smit, Henriëtte A; Picavet, H Susan J

    2006-01-01

    STUDY DESIGN: Cross-sectional study of 11,428 women aged 20-59 years who were included in a postal questionnaire survey in the Dutch general population. OBJECTIVE: To examine how hormonal and reproductive factors are associated with chronic low back pain (LBP) and chronic upper extremity pain (UEP)

  17. The forkhead transcription factor, Foxd1, is necessary for pituitary luteinizing hormone expression in mice.

    Directory of Open Access Journals (Sweden)

    Jason H Gumbel

    Full Text Available The pituitary gland regulates numerous physiological functions including growth, reproduction, temperature and metabolic homeostasis, lactation, and response to stress. Pituitary organogenesis is dependent on signaling factors that are produced in and around the developing pituitary. The studies described in this report reveal that the forkhead transcription factor, Foxd1, is not expressed in the developing mouse pituitary gland, but rather in the mesenchyme surrounding the pituitary gland, which is an essential source of signaling factors that regulate pituitary organogenesis. Loss of Foxd1 causes a morphological defect in which the anterior lobe of the pituitary gland protrudes through the cartilage plate that is developing ventral to the pituitary at embryonic days (e14.5, e16.5, and e18.5. The number of proliferating pituitary cells is increased at e14.5 and e16.5. Loss of Foxd1 also results in significantly decreased levels of Lhb expression at e18.5. This decrease in Lhb expression does not appear to be due to a change in the number of gonadotrope cells in the pituitary gland. Previous studies have shown that loss of the LIM homeodomain factor, Lhx3, which is activated by the FGF signaling pathway, results in loss of LH production. Although there is a difference in Lhb expression in Foxd1 null mice, the expression pattern of LHX3 is not altered in Foxd1 null mice. These studies suggest that Foxd1 is indirectly required for normal Lhb expression and cartilage formation.

  18. Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity

    Czech Academy of Sciences Publication Activity Database

    Křížková, Květoslava; Chrudinová, Martina; Povalová, Anna; Selicharová, Irena; Collinsová, Michaela; Vaněk, Václav; Brzozowski, A. M.; Jiráček, Jiří; Žáková, Lenka

    2016-01-01

    Roč. 55, č. 21 (2016), s. 2903-2913 ISSN 0006-2960 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 Keywords : alanine scanning mutagenesis * high-affinity binding * type 1 IGF receptor Subject RIV: CE - Biochemistry Impact factor: 2.938, year: 2016 http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6b00140

  19. NUTRITIONAL AND HORMONAL FACTORS AFFECTING FRUIT SET IN AVOCADO (Persea americana Mill.)

    OpenAIRE

    D'ASARO, ANTONIO

    2017-01-01

    Under favourable conditions, the avocado sets more fruits than the tree is able to bring to maturity, so that the plant adjusts, during the early stages of development, its ability to nourish them by modifying their number, that is, causing the fruit drop of those who can not maintain their growth rate. Accordingly, carbohydrate availability could be a key factor in the physiological abscission of these fruits. Since this species presents dichogamy, the abscission of fruits has also been attr...

  20. Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

    Science.gov (United States)

    Soliman, Ashraf T; De Sanctis, Vincenzo; Yassin, Mohamed; Adel, Ashraf

    2017-04-28

    Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

  1. Major advances associated with hormone and growth factor regulation of mammary growth and lactation in dairy cows.

    Science.gov (United States)

    Akers, R M

    2006-04-01

    In recent years, the number of researchers interested in mammary development and mammary function in dairy animals has declined. More importantly this cadre of workers has come to rely more than ever on scientists focused on and funded by breast cancer interests to provide fundamental mechanistic and basic cellular insights. Philosophically and practically this is a risky path to better understand, manipulate, and control a national resource as important as the dairy cow. The efficiency, resourcefulness, and dedication of dairy scientists have mirrored the actions of many dairy producers but there are limits. Many of the applications of research, use of bovine somatotropin, management of transition cows, estrus synchronization techniques, and so on, are based on decades-old scientific principles. Specific to dairy, do rodents or breast cancer cell lines adequately represent the dairy cow? Will these results inspire the next series of lactation-related dairy improvements? These are key unanswered questions. Study of the classic mammogenic and lactogenic hormones has served dairy scientists well. But there is an exciting, and bewildering universe of growth factors, transcription factors, receptors, intracellular signaling intermediates, and extracellular molecules that must ultimately interact to determine the size of the mature udder and the functional capacity of mammary gland in the lactating cow. We can only hope that enough scientific, fiscal, and resource scraps fall from the biomedical research banquet table to allow dairy-focused mammary gland research to continue.

  2. Low Levels of Sex Hormone-Binding Globulin Constitute an Independent Risk Factor for Arterial Stiffness in Korean Women

    Directory of Open Access Journals (Sweden)

    Kunhee Han

    2017-01-01

    Full Text Available The association between sex hormone-binding globulin (SHBG and arterial stiffness in women is not conclusive. In addition, obesity might also be involved in the relationship between SHBG and atherosclerosis. The aim of this study was to determine the relationship between SHBG and arterial stiffness in association with central obesity in women. This cross-sectional study included 381 women who participated in the health checkup programs in one hospital. The brachial-ankle pulse wave velocity (baPWV was measured as a marker for arterial stiffness. A negative correlation was observed between SHBG levels and baPWV (rho = −0.281. The relationship was significant even after adjusting for potential confounders (beta = −0.087 in fully adjusted model. After considering the interaction between central obesity and SHBG levels, the significant association was evident only in obese women (P for interaction = 0.025. Adjustment for a 10-year atherosclerotic cardiovascular disease (ASCVD risk scores, instead of each cardiovascular risk factor individually, did not affect the significance of the relationship between SHBG levels and baPWV. Serum levels of SHBG were negatively associated with arterial stiffness independent of cardiovascular risk factors or 10-year ASCVD risk scores in Korean women. The relationship may be potentiated by central obesity.

  3. Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2007-01-01

    In the present study, we report the upregulation of functional IGF-2Rs in cells overexpressing growth hormone (GH). EL4 lymphoma cells stably transfected with an rGH cDNA overexpression vector (GHo) exhibited an increase in the binding of (125)I-IGF-2 with no change in the binding affinity compared to vector alone controls. An increase in the expression of the insulin-like growth factor-2 receptor (IGF-2R) in cells overexpressing GH was confirmed by Western blot analysis and IGF-2R promoter luciferase assays. EL4 cells produce insulin-like growth factor-2 (IGF-2) as detected by the reverse transcription-polymerase chain reaction (RT-PCR); however, no IGF-2 protein was detected by Western analysis. The increase in the expression of the IGF-2R resulted in greater levels of IGF-2 uptake in GHo cells compared to vector alone controls. The data suggest that one of the consequences of the overexpression of GH is an increase in the expression of the IGF-2R.

  4. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Min-Gu Kang

    2014-01-01

    Full Text Available We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM. So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1 pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL group, the hazard ratio (HR for overall survival was higher for group with high PTH level (≥68.3 pg/mL (HR, 1.710. Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P=0.056. Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.

  5. Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

    DEFF Research Database (Denmark)

    Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn

    2017-01-01

    Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although...

  6. Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer in Europe

    International Nuclear Information System (INIS)

    Jerusalem, Guy; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Ricci, Jean-François; Andre, Fabrice

    2015-01-01

    Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). Total direct costs across the first 3 treatment lines were approximately €10 000 to €14 000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2– advanced breast cancer. The online version of this article (doi:10.1186/s12885-015-1762-3) contains supplementary material, which is available to authorized users

  7. Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats.

    Science.gov (United States)

    Kim, Soo-Jeong; Ju, Anes; Lim, Seul-Gi; Kim, Dai-Jin

    2013-11-13

    Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated. Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group. These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels. © 2013. Published by Elsevier Inc. All rights reserved.

  8. Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells

    DEFF Research Database (Denmark)

    Billestrup, Nils; Mitchell, R L; Vale, W

    1987-01-01

    GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal...... induction of c-fos mRNA was observed 20-60 min after stimulation with 5 nM GRF, returning to basal levels after 2 h. Somatostatin-14 (5 nM) partially inhibited the GRF induced c-fos expression. Forskolin and phorbol 12, 13 dibutyrate induced c-fos gene in cultured primary pituitary cells with similar...

  9. [Metabolic and hemodynamic effects of the growth hormone system - insulin-like growth factor].

    Science.gov (United States)

    Manhylova, T A; Gafarova, N H

    2015-01-01

    Significant congenital deficiency of growth factor (GF) results in pituitary nanism (dwarfism) and its substantial excess is accompanied by the development of gigantism or acromegaly. Its impact on the growth of the whole body or its individual parts is impossible without affecting metabolic processes and hemodynamic parameters. A number of investigations have proven that GF has a direct lipolytic effect: adequate replacement therapy for pituitary nanism gives rise to a reduction in fat depots. Since the concentration of GF is lower in obesity, Whether it may be used to treat this abnormality is considered.

  10. Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor

    DEFF Research Database (Denmark)

    Stefaneanu, L; Kovacs, K; Horvath, E

    1989-01-01

    The effect of protracted GH-releasing factor (GRF) stimulation on adenohypophysial morphology was investigated in six mice transgenic for human GRF (hGRF). All animals had significantly higher plasma levels of GH and GRF and greater body weights than controls. Eight-month-old mice were killed...... of their ultrastructural features, contained secretory granules heavily labeled for GH by immunogold technique; PRL labeling varied from cell to cell, with the predominance of a weak immunostaining and was colocalized with GH in secretory granules. These results indicate that chronic exposure to GRF excess leads...

  11. miR-1338-5p Modulates Growth Hormone Secretion and Glucose Utilization by Regulating ghitm in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus).

    Science.gov (United States)

    Qiang, Jun; Bao, Jing Wen; Li, Hong Xia; Chen, De Ju; He, Jie; Tao, Yi Fan; Xu, Pao

    2017-01-01

    MicroRNAs (miRNAs) are endogenous, non-coding small RNA molecules about 22 nt in length, which could regulate the expressions of target genes and participate in growth and development of organisms. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus ) is an important economic freshwater species in China and the growth performance is one of the main breeding indicators. Growth hormone inducible transmembrane protein ( ghitm ) plays an important role in growth and development of both mammals and invertebrates; however, little studies have been reported on fish. Our previous experiments indicated that miR-1338-5p expression may be negatively correlated with ghitm expression. In this study, we firstly used qRT-PCR and northern blot to verify the expression of miR-1338-5p and ghitm , and determined the binding site of miR-1338-5p in the ghitm 3'-untranslated region (UTR) by luciferase reporter assay. Secondly, juveniles GIFT injected with miR-1338-5p antagomir were used to analyze the regulatory function of the miR-1338-5p- ghitm pair in vivo . The results showed that the ghitm 3'-UTR was complementary to the 5' 2-8-nt site of miR-1338-5p. Inhibition of miR-1338-5p promoted ghitm expression in the pituitary and liver of GIFT. ghitm could interfere in the growth hormone (Gh)-growth hormone receptor (Ghr)-insulin-like growth factor (Igf) signaling pathway by competing with the ghr1 for combination with Gh, and then reduce the growth of GIFT. Moreover, the reduction of Gh in serum may regulate insulin secretion and result in the increasing sugar and fat storage in serum and liver. Our results suggest that miR-1338-5p participates in the growth and development of GIFT through the regulation of ghitm , which provides theoretical support for the study of the fish growth mechanism.

  12. The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators, and parathyroid hormone on bone remodeling in osteoporosis

    Directory of Open Access Journals (Sweden)

    Silvia Migliaccio

    2007-04-01

    Full Text Available Silvia Migliaccio, Marina Brama, Giovanni SperaCattedra di Medicina Interna, Dipartimento di Fisiopatologia Medica, Università degli Studi di Roma “La Sapienza”, Italy Abstract: Osteoporosis is a skeletal metabolic disease characterized by a compromised bone fragility, leading to an increased risk of developing spontaneous and traumatic fractures. Osteoporosis is considered a multifactorial disease and fractures are the results of several different risk factors both extra- and intraskeletal. Thus bone fragility can be the end point of several different causes: a failure to reach an optimal peak bone mass during growth; b excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration; c inadequate formation upon an increased resorption during the process of bone remodeling. The pharmacological therapeutical options, available to date, are directed on prevention of fractures. The aim of this paper is to describe the activities and the mechanisms of action, as known at present, of the most used therapies for osteoporosis and their clinical implications. Improvement of knowledge in this field will allow us to further improve therapeutical choices and pharmacological interventions.Keywords: Osteoporosis, estrogens, bisphosphonates, SERMS, teriparatide, mechanism of action, fracture

  13. Relationship among circulating anti-Müllerian hormone, insulin like growth factor 1, cadmium and superovulatory response in dairy cows.

    Science.gov (United States)

    Abdel Aziz, R L; Khalil, A A Y; Abdel-Wahab, A; Hassan, N Y; Abdel-Hamied, E; Kasimanickam, R K

    2017-09-15

    The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced. Published by Elsevier Inc.

  14. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  15. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure

    DEFF Research Database (Denmark)

    Nielsen, R H; Clausen, N M; Schjerling, P

    2014-01-01

    transgenic mice that expressed bovine GH (bGH) and had high circulating levels of GH and IGF-I, 2) dwarf mice with a disrupted GH receptor gene (GHR-/-) leading to GH resistance and low circulating IGF-I, and 3) a wild-type control group (CTRL). We measured the ultra-structure, collagen content and m......The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important stimulator of collagen synthesis in connective tissue, but the effect of chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon unit is not known. We studied three groups of mice; 1) giant......-/- mice had significantly lower collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA expression of IGF-I isoforms and collagen types I and III in muscle compared to CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH mice was generally high in both tendon...

  16. Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 Regulates Xylem Development and Growth by a Conserved Mechanism That Modulates Hormone Signaling1[W][OPEN

    Science.gov (United States)

    Grienenberger, Etienne; Douglas, Carl J.

    2014-01-01

    Despite a strict conservation of the vascular tissues in vascular plants (tracheophytes), our understanding of the genetic basis underlying the differentiation of secondary cell wall-containing cells in the xylem of tracheophytes is still far from complete. Using coexpression analysis and phylogenetic conservation across sequenced tracheophyte genomes, we identified a number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose expression is correlated with secondary cell wall deposition. Among these, the Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted protein of 24 kD with no annotated functional domains but containing domains that are highly conserved in tracheophytes. Here, we show that the VUP1 expression pattern, determined by promoter-β-glucuronidase reporter gene expression, is associated with vascular tissues, while vup1 loss-of-function mutants exhibit collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1 caused dramatic and pleiotropic developmental defects, including severe dwarfism, dark green leaves, reduced apical dominance, and altered photomorphogenesis, resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP homologs from multiple tracheophyte species induced similar defects. Whole-genome transcriptome analysis revealed that overexpression of VUP1 represses the expression of many brassinosteroid- and auxin-responsive genes. Additionally, deletion constructs and site-directed mutagenesis were used to identify critical domains and amino acids required for VUP1 function. Altogether, our data suggest a conserved role for VUP1 in regulating secondary wall formation during vascular development by tissue- or cell-specific modulation of hormone signaling pathways. PMID:24567189

  17. Effect of rejuvenation hormones on spermatogenesis.

    Science.gov (United States)

    Moss, Jared L; Crosnoe, Lindsey E; Kim, Edward D

    2013-06-01

    To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of spermatogenesis. Review of published literature. Not applicable. Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies. None. Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis. Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG) therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring children at a later age may be unaware of the side-effect profile of hormones used at rejuvenation centers. Testosterone and anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1 (IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to have significant negative effects on sperm production, but quality data are lacking. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Identification and expression analysis of ERF transcription factor genes in petunia during flower senescence and in response to hormone treatments.

    Science.gov (United States)

    Liu, Juanxu; Li, Jingyu; Wang, Huinan; Fu, Zhaodi; Liu, Juan; Yu, Yixun

    2011-01-01

    Ethylene-responsive element-binding factor (ERF) genes constitute one of the largest transcription factor gene families in plants. In Arabidopsis and rice, only a few ERF genes have been characterized so far. Flower senescence is associated with increased ethylene production in many flowers. However, the characterization of ERF genes in flower senescence has not been reported. In this study, 13 ERF cDNAs were cloned from petunia. Based on the sequence characterization, these PhERFs could be classified into four of the 12 known ERF families. Their predicted amino acid sequences exhibited similarities to ERFs from other plant species. Expression analyses of PhERF mRNAs were performed in corollas and gynoecia of petunia flower. The 13 PhERF genes displayed differential expression patterns and levels during natural flower senescence. Exogenous ethylene accelerates the transcription of the various PhERF genes, and silver thiosulphate (STS) decreased the transcription of several PhERF genes in corollas and gynoecia. PhERF genes of group VII showed a strong association with the rise in ethylene production in both petals and gynoecia, and might be associated particularly with flower senescence in petunia. The effect of sugar, methyl jasmonate, and the plant hormones abscisic acid, salicylic acid, and 6-benzyladenine in regulating the different PhERF transcripts was investigated. Functional nuclear localization signal analyses of two PhERF proteins (PhERF2 and PhERF3) were carried out using fluorescence microscopy. These results supported a role for petunia PhERF genes in transcriptional regulation of petunia flower senescence processes.

  19. Health care factors associated with survival among women with breast cancer on hormone therapy in Rio de Janeiro, Brazil, 2004 – 2010

    Directory of Open Access Journals (Sweden)

    Cláudia de Brito

    Full Text Available ABSTRACT Objectives To better understand the role that health care plays in breast cancer survival by investigating the effects that hormone therapy adherence and other select health care variables, adjusted for clinical and sociodemographic factors, had among a population of women in Rio de Janeiro, Brazil. Methods This was a longitudinal study based on secondary data of 5 861 women treated with hormone therapy (tamoxifen or aromatase inhibitors at the National Cancer Institute of Brazil (INCA, from 1 January 2004 – 29 October 2010. Four different sources of data were integrated for analysis: INCA Pharmacy Sector Dispensation System; Hospital-based Cancer Registry; Integrated Hospital System and INCA Absolute System; and Mortality Information System. Analyses explored the effects of adherence to hormone therapy, disease care aspects, and sociodemographic, behavioral, and clinical variables, on the time of survival, using Kaplan-Meier and Cox proportional hazards models. Results The general survival rate was 94% in the first year after initiation of hormone therapy, and 71% in the fifth year. The Cox model indicated a higher hazard of death among women smokers, with more hospitalizations, more exams, and, among those who used, who used only aromatase inhibitors, as hormone therapy modality. The hazard was lower among women with a partner (stable relationship, a high school or college education a family history of cancer, and those who were treated by a mastologist, oncologist, and/or psychotherapist, who underwent surgery, and who adhered to hormone therapy. Conclusions The study indicated more vulnerable sub-groups and the aspects of care that provide best results, bringing new knowledge to improve assistance to this group of women.

  20. Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

    Science.gov (United States)

    Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

    2014-12-01

    Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Digital gene expression analysis of male and female bud transition in Metasequoia reveals high activity of MADS-box transcription factors and hormone-mediated sugar pathways.

    Science.gov (United States)

    Zhao, Ying; Liang, Haiying; Li, Lan; Tang, Sha; Han, Xiao; Wang, Congpeng; Xia, Xinli; Yin, Weilun

    2015-01-01

    Metasequoia glyptostroboides is a famous redwood tree of ecological and economic importance, and requires more than 20 years of juvenile-to-adult transition before producing female and male cones. Previously, we induced reproductive buds using a hormone solution in juvenile Metasequoia trees as young as 5-to-7 years old. In the current study, hormone-treated shoots found in female and male buds were used to identify candidate genes involved in reproductive bud transition in Metasequoia. Samples from hormone-treated cone reproductive shoots and naturally occurring non-cone setting shoots were analyzed using 24 digital gene expression (DGE) tag profiles using Illumina, generating a total of 69,520 putative transcripts. Next, 32 differentially and specifically expressed transcripts were determined using quantitative real-time polymerase chain reaction, including the upregulation of MADS-box transcription factors involved in male bud transition and flowering time control proteins involved in female bud transition. These differentially expressed transcripts were associated with 243 KEGG pathways. Among the significantly changed pathways, sugar pathways were mediated by hormone signals during the vegetative-to-reproductive phase transition, including glycolysis/gluconeogenesis and sucrose and starch metabolism pathways. Key enzymes were identified in these pathways, including alcohol dehydrogenase (NAD) and glutathione dehydrogenase for the glycolysis/gluconeogenesis pathway, and glucanphosphorylase for sucrose and starch metabolism pathways. Our results increase our understanding of the reproductive bud transition in gymnosperms. In addition, these studies on hormone-mediated sugar pathways increase our understanding of the relationship between sugar and hormone signaling during female and male bud initiation in Metasequoia.

  2. Digital gene expression analysis of male and female bud transition in Metasequoia reveals high activity of MADS-box transcription factors and hormone-mediated sugar pathways

    Directory of Open Access Journals (Sweden)

    Ying eZhao

    2015-06-01

    Full Text Available Metasequoiaglyptostroboidies is a famous redwood tree of ecological and economic importance, and requires more than 20 years of juvenile-to-adult transition before producing female and male cones. Previously, we induced reproductive buds using a hormone solution in juvenile Metasequoia trees as young as5-to-7years old. In the current study, hormone-treated shoots found in female and male buds were used to identify candidate genes involved in reproductive bud transition in Metasequoia. Samples from hormone-treated cone reproductive shoots and naturally occurring non-cone setting shoots were analyzed using 24 digital gene expression (DGE tag profiles using Illumina, generating a total of 69,520 putative transcripts. Next, 32 differentially and specifically expressed transcripts were determined using quantitative real-time polymerase chain reaction, including the upregulation of MADS-box transcription factors involved in male bud transition and flowering time control proteins involved in female bud transition. These differentially expressed transcripts were associated with 243 KEGG pathways. Among the significantly changed pathways, sugar pathways were mediated by hormone signals during the vegetative-to-reproductive phase transition, including glycolysis/gluconeogenesis and sucrose and starch metabolism pathways. Key enzymes were identified in these pathways, including alcohol dehydrogenase (NAD and glutathione dehydrogenase for the glycolysis/gluconeogenesis pathway, and glucanphosphorylase for sucrose and starch metabolism pathways. Our results increase our understanding of the reproductive bud transition in gymnosperms. In addition, these studies on hormone-mediated sugar pathways increase our understanding of the relationship between sugar and hormone signaling during female and male bud initiation in Metasequoia.

  3. Direct Regulation of Mitochondrial RNA Synthesis by Thyroid Hormone

    Science.gov (United States)

    Enríquez, José A.; Fernández-Silva, Patricio; Garrido-Pérez, Nuria; López-Pérez, Manuel J.; Pérez-Martos, Acisclo; Montoya, Julio

    1999-01-01

    We have analyzed the influence of in vivo treatment and in vitro addition of thyroid hormone on in organello mitochondrial DNA (mtDNA) transcription and, in parallel, on the in organello footprinting patterns at the mtDNA regions involved in the regulation of transcription. We found that thyroid hormone modulates mitochondrial RNA levels and the mRNA/rRNA ratio by influencing the transcriptional rate. In addition, we found conspicuous differences between the mtDNA dimethyl sulfate footprinting patterns of mitochondria derived from euthyroid and hypothyroid rats at the transcription initiation sites but not at the mitochondrial transcription termination factor (mTERF) binding region. Furthermore, direct addition of thyroid hormone to the incubation medium of mitochondria isolated from hypothyroid rats restored the mRNA/rRNA ratio found in euthyroid rats as well as the mtDNA footprinting patterns at the transcription initiation area. Therefore, we conclude that the regulatory effect of thyroid hormone on mitochondrial transcription is partially exerted by a direct influence of the hormone on the mitochondrial transcription machinery. Particularly, the influence on the mRNA/rRNA ratio is achieved by selective modulation of the alternative H-strand transcription initiation sites and does not require the previous activation of nuclear genes. These results provide the first functional demonstration that regulatory signals, such as thyroid hormone, that modify the expression of nuclear genes can also act as primary signals for the transcriptional apparatus of mitochondria. PMID:9858589

  4. Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain.

    Science.gov (United States)

    Sinclair, Duncan; Purves-Tyson, Tertia D; Allen, Katherine M; Weickert, Cynthia Shannon

    2014-04-01

    Adolescence is a developmental period of complex neurobiological change and heightened vulnerability to psychiatric illness. As a result, understanding factors such as sex and stress hormones which drive brain changes in adolescence, and how these factors may influence key neurotransmitter systems implicated in psychiatric illness, is paramount. In this review, we outline the impact of sex and stress hormones at adolescence on dopamine neurotransmission, a signaling pathway which is critical to healthy brain function and has been implicated in psychiatric illness. We review normative developmental changes in dopamine, sex hormone, and stress hormone signaling during adolescence and throughout postnatal life, then highlight the interaction of sex and stress hormones and review their impacts on dopamine neurotransmission in the adolescent brain. Adolescence is a time of increased responsiveness to sex and stress hormones, during which the maturing dopaminergic neural circuitry is profoundly influenced by these factors. Testosterone, estrogen, and glucocorticoids interact with each other and have distinct, brain region-specific impacts on dopamine neurotransmission in the adolescent brain, shaping brain maturation and cognitive function in adolescence and adulthood. Some effects of stress/sex hormones on cortical and subcortical dopamine parameters bear similarities with dopaminergic abnormalities seen in schizophrenia, suggesting a possible role for sex/stress hormones at adolescence in influencing risk for psychiatric illness via modulation of dopamine neurotransmission. Stress and sex hormones may prove useful targets in future strategies for modifying risk for psychiatric illness.

  5. Gonadal Hormones and Retinal Disorders: A Review

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2018-03-01

    Full Text Available AimGonadal hormones are essential for reproductive function, but can act on neural and other organ systems, and are probably the cause of the large majority of known sex differences in function and disease. The aim of this review is to provide evidence for this hypothesis in relation to eye disorders and to retinopathies in particular.MethodsEpidemiological studies and research articles were reviewed.ResultsAnalysis of the biological basis for a relationship between eye diseases and hormones showed that estrogen, androgen, and progesterone receptors are present throughout the eye and that these steroids are locally produced in ocular tissues. Sex hormones can have a neuroprotective action on the retina and modulate ocular blood flow. There are differences between the male and the female retina; moreover, sex hormones can influence the development (or not of certain disorders. For example, exposure to endogenous estrogens, depending on age at menarche and menopause and number of pregnancies, and exposure to exogenous estrogens, as in hormone replacement therapy and use of oral contraceptives, appear to protect against age-related macular degeneration (both drusenoid and neurovascular types, whereas exogenous testosterone therapy is a risk factor for central serous chorioretinopathy. Macular hole is more common among women than men, particularly in postmenopausal women probably owing to the sudden drop in estrogen production in later middle age. Progestin therapy appears to ameliorate the course of retinitis pigmentosa. Diabetic retinopathy, a complication of diabetes, may be more common among men than women.ConclusionWe observed a correlation between many retinopathies and sex, probably as a result of the protective effect some gonadal hormones may exert against the development of certain disorders. This may have ramifications for the use of hormone therapy in the treatment of eye disease and of retinal disorders in particular.

  6. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  7. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  8. Insulin-like growth factor-I as a possible hormonal mediator of nutritional regulation of reproduction in cattle.

    Science.gov (United States)

    Zulu, Victor Chisha; Nakao, Toshihiko; Sawamukai, Yutaka

    2002-08-01

    The current review aims to establish insulin-like growth factor-1 (IGF-I) as the factor that signals nutritional status to the reproductive axis, and show that assessment of IGF-I in blood early postpartum during the negative energy balance (NEB) period could be used to predict both nutritional and reproductive status in dairy cattle. The review also explores the effect of nutritional status on circulating IGF-I concentrations and the endocrine role of IGF-I on the reproductive axis. IGF-I plays an important role in gonadotropin-induced folliculogenesis, ovarian steroidogenesis and corpus luteum (CL) function. It also modulates pituitary and hypothalamus function. IGF-I clearly has an endocrine role on the reproductive axis. Severe under nutrition significantly reduces plasma IGF-I concentrations. During the critical period of NEB in high yielding dairy cattle early postpartum, IGF-I concentrations are low in blood and its levels are positively correlated to energy status and reproductive function during this period. Changes in circulating IGF-I immediately postpartum may help predict both nutritional and reproductive status in dairy cattle. IGF-I is therefore one of the long sought factors that signal nutritional status to the reproductive axis.

  9. SCALE FACTOR DETERMINATION METHOD OF ELECTRO-OPTICAL MODULATOR IN FIBER-OPTIC GYROSCOPE

    Directory of Open Access Journals (Sweden)

    A. S. Aleynik

    2016-05-01

    Full Text Available Subject of Research. We propose a method for dynamic measurement of half-wave voltage of electro-optic modulator as part of a fiber optic gyroscope. Excluding the impact of the angular acceleration o​n measurement of the electro-optical coefficient is achieved through the use of homodyne demodulation method that allows a division of the Sagnac phase shift signal and an auxiliary signal for measuring the electro-optical coefficient in the frequency domain. Method. The method essence reduces to decomposition of step of digital serrodyne modulation in two parts with equal duration. The first part is used for quadrature modulation signals. The second part comprises samples of the auxiliary signal used to determine the value of the scale factor of the modulator. Modeling is done in standalone model, and as part of a general model of the gyroscope. The applicability of the proposed method is investigated as well as its qualitative and quantitative characteristics: absolute and relative accuracy of the electro-optic coefficient, the stability of the method to the effects of angular velocities and accelerations, method resistance to noise in actual devices. Main Results. The simulation has showed the ability to measure angular velocity changing under the influence of angular acceleration, acting on the device, and simultaneous measurement of electro-optical coefficient of the phase modulator without interference between these processes. Practical Relevance. Featured in the paper the ability to eliminate the influence of the angular acceleration on the measurement accuracy of the electro-optical coefficient of the phase modulator will allow implementing accurate measurement algorithms for fiber optic gyroscopes resistant to a significant acceleration in real devices.

  10. 3D conformal radiation therapy and hormonal therapy for localized prostate cancer: Is age a limiting factor?

    International Nuclear Information System (INIS)

    Faure, A.; Negrea, T.; Lechevallier, E.; Coulange, C.; Murraciole, X.; Jouvea, E.; Sambuca, R.; Cowen, D.

    2011-01-01

    No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9 300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71 92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67 80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P ≡ ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients. (authors)

  11. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone

    Science.gov (United States)

    Bikle, Daniel D.; Sakata, Takeshi; Leary, Colin; Elalieh, Hashem; Ginzinger, David; Rosen, Clifford J.; Beamer, Wesley; Majumdar, Sharmila; Halloran, Bernard P.

    2002-01-01

    Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.

  12. Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Grønbaek, M; Main, K

    1993-01-01

    was significantly higher in patients than in the healthy controls (p liver function assessed by modified Child-Turcotte score (p encephalopathy (p ...Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis...... and correlated with liver function (p

  13. Crew Factors in Flight Operations XV: Alertness Management in General Aviation Education Module

    Science.gov (United States)

    Rosekind, Mark R.; Co, Elizabeth L.; Neri, David F.; Oyung, Raymond L.; Mallis, Melissa M.; Cannon, Mary M. (Technical Monitor)

    2002-01-01

    Regional operations encompass a broad range of pilots and equipment. This module is intended to help all those involved in regional aviation, including pilots, schedulers, dispatchers, maintenance technicians, policy makers, and others, to understand the physiological factors underlying fatigue, how flight operations affect fatigue, and what can be done to counteract fatigue and maximize alertness and performance in their operations. The overall purpose of this module is to promote aviation safety, performance, and productivity. It is intended to meet three specific objectives: (1) to explain the current state of knowledge about the physiological mechanisms underlying fatigue; (2) to demonstrate how this knowledge can be applied to improving flight crew sleep, performance, and alertness; and (3) to offer strategies for alertness management. Aviation Safety Reporting System (ASRS) and National Transportation Safety Board (NISH) reports are used throughout this module to demonstrate that fatigue is a safety issue in the regional operations community. The appendices at the end of this module include the ASRS reports used for the examples contained in this publication, brief introductions to sleep disorders and relaxation techniques, summaries of relevant NASA publications, and a list of general readings on sleep, sleep disorders, and circadian rhythms.

  14. Crew Factors in Flight Operations XIV: Alertness Management in Regional Flight Operations Education Module

    Science.gov (United States)

    Rosekind, Mark R.; Co, Elizabeth L.; Neri, David F.; Oyung, Raymond L.; Mallis, Melissa M.

    2002-01-01

    Regional operations encompass a broad range of pilots and equipment. This module is intended to help all those involved in regional aviation, including pilots, schedulers, dispatchers, maintenance technicians, policy makers, and others, to understand the physiological factors underlying fatigue, how flight operations affect fatigue, and what can be done to counteract fatigue and maximize alertness and performance in their operations. The overall purpose of this module is to promote aviation safety, performance, and productivity. It is intended to meet three specific objectives: (1) to explain the current state of knowledge about the physiological mechanisms underlying fatigue; (2) to demonstrate how this knowledge can be applied to improving flight crew sleep, performance, and alertness; and (3) to offer strategies for alertness management. Aviation Safety Reporting System (ASRS) and National Transportation Safety Board (NISH) reports are used throughout this module to demonstrate that fatigue is a safety issue in the regional operations community. The appendices at the end of this module include the ASRS reports used for the examples contained in this publication, brief introductions to sleep disorders and relaxation techniques, summaries of relevant NASA publications, and a list of general readings on sleep, sleep disorders, and circadian rhythms.

  15. Digoxin-like immunoreactivity, endogeneous cardiac glycoside-like factors (s) and natriuretic hormone. More than a hypothesis. Review article

    Energy Technology Data Exchange (ETDEWEB)

    Clerico, A

    1987-01-01

    Endogenous factors crossreacting with antidigoxin antibodies (digoxin-like immunoreactive substances=DLIS) have been found in several tissues and body fluids of animals and humans, using commercially avaiable digoxin RIA or EIA methods. Detectable DLIS concentration were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that DLIS could be a substance with low molecular weight. Experimental studies and theoretical consideration suggest that DLIS, in addition to reacting with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na/sup +//K/sup +/ ATPase (sodium pump). Therefore, it has been suggested that DLSI is an endogeneous modulator of the membrane sodium-potassium pump and it could play a role in the regulation of fluid and electrolytes muscular tone of myocardial and also in pathogenesis of hypertension. 91 refs.

  16. 100-Gb/s InP DP-IQ modulator for small-form-factor pluggable coherent transceivers

    Science.gov (United States)

    Kikuchi, Nobuhiro; Ogiso, Yoshihiro; Yamada, Eiichi

    2016-02-01

    We developed a compact InP-based DP-IQ modulator for small-form-factor pluggable coherent transceivers. The modulator achieves 112-Gb/s DP-QPSK modulation with a driving voltage of 6 Vppd. In addition, it provides 86-Gb/s DP-16 QAM signal generation and 240-km transmission with negligible degradation of BER performance. The halfwavelength voltage of our recent device is 1.9 V, and a high median extinction ratio of over 32 dB was achieved for more than 1,400 child MZ modulators. We have also proposed an athermal InP-based twin IQ modulator that enables us to use a modulator in a TEC-free operation. It contributes to lowering the power consumption of transceivers. Under a constant driving condition, there is little change in 56-Gb/s x 2 QPSK modulation characteristics in the range of 20 to 80°C.

  17. Gastrointestinal hormone research - with a Scandinavian annotation

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2015-01-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones...... as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions...

  18. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Science.gov (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  19. Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

    Science.gov (United States)

    Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

    2018-04-03

    High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

  20. Leptin stimulates hepatic growth hormone receptor and insulin-like growth factor gene expression in a teleost fish, the hybrid striped bass.

    Science.gov (United States)

    Won, Eugene T; Douros, Jonathan D; Hurt, David A; Borski, Russell J

    2016-04-01

    Leptin is an anorexigenic peptide hormone that circulates as an indicator of adiposity in mammals, and functions to maintain energy homeostasis by balancing feeding and energy expenditure. In fish, leptin tends to be predominantly expressed in the liver, another important energy storing tissue, rather than in fat depots as it is in mammals. The liver also produces the majority of circulating insulin-like growth factors (IGFs), which comprise the mitogenic component of the growth hormone (GH)-IGF endocrine growth axis. Based on similar regulatory patterns of leptin and IGFs that we have documented in previous studies on hybrid striped bass (HSB: Morone saxatilis×Morone chrysops), and considering the co-localization of these peptides in the liver, we hypothesized that leptin might regulate the endocrine growth axis in a manner that helps coordinate somatic growth with energy availability. Using a HSB hepatocyte culture system to simulate autocrine or paracrine exposure that might occur within the liver, this study examines the potential for leptin to modulate metabolism and growth through regulation of IGF gene expression directly, or indirectly through the regulation of GH receptors (GHR), which mediate GH-induced IGF expression. First, we verified that GH (50nM) has a classical stimulatory effect on IGF-1 and additionally show it stimulates IGF-2 transcription in hepatocytes. Leptin (5 and/or 50nM) directly stimulated in vitro GHR2 gene expression within 8h of exposure, and both GHR1 and GHR2 as well as IGF-1 and IGF-2 gene expression after 24h. Cells were then co-incubated with submaximal concentrations of leptin and GH (25nM each) to test if they had a synergistic effect on IGF gene expression, possibly through increased GH sensitivity following GHR upregulation by leptin. In combination, however, the treatments only had an additive effect on stimulating IGF-1 mRNA despite their capacity to increase GHR mRNA abundance. This suggests that leptin's stimulatory

  1. Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

    OpenAIRE

    Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C

    1996-01-01

    Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...

  2. Growth hormone abuse and bodybuilding as aetiological factors in the development of bilateral internal laryngocoeles. A case report.

    Science.gov (United States)

    Moor, James W; Khan, M Iqbal J

    2005-07-01

    A 36-year-old man presented with hoarseness and stridor. He was an elite professional bodybuilder and admitted to having abusing anabolic steroids and growth hormone in the recent past. A CT scan showed bilateral laryngocoeles. The patient was initially managed with intravenous corticosteroids and broad-spectrum antibiotics, and the stridor resolved sufficiently to permit discharge from the hospital. He proceeded to undergo endoscopic marsupialisation of his laryngocoeles and to date has made a full recovery. This is the first reported case where anabolic steroid and growth hormone abuse combined with an elite bodybuilder's exercise regime has been implicated in the aetiology of bilateral laryngocoeles.

  3. Hormonal profile in children with isolated hypospadias associates better with comprehensive score of local anatomical factors as compared to meatal location or degree of chordee

    Directory of Open Access Journals (Sweden)

    Simmi K Ratan

    2014-01-01

    Full Text Available Background: To evaluate if hormonal profile of children with isolated hypospadias (IH associates better with comprehensive local anatomical factor score (LAFS than with clinically adjudged urethral meatus location or severity of chordee/k.j. Material and Methods: Ninety-nine children with IH were enrolled, as per inclusion criteria. Meatal location was recorded at first clinical examination in OPD; while LAFS was computed per-operatively using indigenously devised scale, except for neonates. Hypospadiacs were first classified into three standard meatal based groups and subsequently into LAFS based two groups (≤19, >19. For all participants, pre HCG and post HCG (96 hour post- injection estimation of serum gonadotropins, DHEA-S, estrogen (E, progesterone (P, testosterone (T and Dihydrotestosterone (DHT was done. Statistical tests were applied to assess significance of hormonal levels with respect to meatal location, chordee and LAFS. Results: Only FSH levels differed significantly among meatal based groups; while among LAFS groups, multiple hormonal differences were noted; with poor LAFS associated significantly with higher FSH, LH and lower E, T/DHT. Children with severe degree of chordee had poorer T output and a significantly lower LAFS as compared to those with moderate/mild chordee. Conclusion: Serotoli cell dysfunction, indirectly indicated by high FSH was found among midpenile hypospadiacs and those with poorer LAFS. Since groups based on LAFS revealed multiple intergroup hormonal differences than what was seen for meatal/chordee based groups; LAFS should be considered a better guide for prognostication and for deciding about hormonal supplementation. Lower androgenic output was particularly noted in children with severe chordee.

  4. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

    Science.gov (United States)

    Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

    2002-03-01

    Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

  5. Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Il Yong Chung

    Full Text Available The aim of this study was to determine the relationship between the body mass index (BMI at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS and breast-cancer-specific survival (BCSS outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029, and BCSS (P = 0.013 in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48 and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99. In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19 and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44. Being underweight (BMI < 18.50 kg/m2 with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95 and BCSS (HR = 2.24, 95% CI = 1.12-4.47. There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

  6. Hormone action. Part I. Peptide hormones

    International Nuclear Information System (INIS)

    Birnbaumer, L.; O'Malley, B.W.

    1985-01-01

    The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

  7. An Analysis of the Influence of Selected Genetic and Hormonal Factors on the Occurrence of Depressive Symptoms in Late-Reproductive-Age Women

    Directory of Open Access Journals (Sweden)

    Anna Jurczak

    2015-03-01

    Full Text Available Background: The aim of this study was to analyze the influence of genetic and hormonal factors on incidences of depressive symptoms in late-reproductive-age women. Methods: The study was performed using the Beck Depression Inventory, the PCR, and genetic tests of 347 healthy late-reproductive-age Polish women. Results: The relationship between the level of anti-Müllerian hormone (AMH and depressive symptoms was not statistically significant (p > 0.05. Increases in age and FSH levels were accompanied by a decrease in AMH level in a significant way (p < 0.05. There were no statistically significant relationships between the distribution of genotypes and the frequency of alleles of the investigated polymorphisms and depressive symptoms according to the Beck Depression Inventory. Conclusions: (1 The presence of the s/s genotype of the 5-HTTLPR polymorphism in the serotonin transporter promoter region and the 3/3 genotype of the 30-bp VNTR polymorphism in the monoamine oxidase A promoter region does not contribute to the development of depressive symptoms in late-reproductive-age women. (2 A relationship between the level of anti-Müllerian hormone and depressive symptoms was not confirmed in the group of healthy late-reproductive-age women. (3 AMH level correlates negatively with FSH level and age, which confirms that AMH can be regarded as a factor reflecting the ovarian reserve.

  8. Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia

    NARCIS (Netherlands)

    van Beveren, N. J. M.; Schwarz, E.; Noll, R.; Guest, P. C.; Meijer, C.; de Haan, L.; Bahn, S.

    2014-01-01

    Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the

  9. Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases

    Science.gov (United States)

    Markey, Keira A; Uldall, Maria; Botfield, Hannah; Cato, Liam D; Miah, Mohammed A L; Hassan-Smith, Ghaniah; Jensen, Rigmor H; Gonzalez, Ana M; Sinclair, Alexandra J

    2016-01-01

    Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation. Despite occurring almost exclusively in obese women, there have been a few studies evaluating the mechanisms by which hormones and adipokines exert their effects on ICP regulation in IIH. Research involving 11β-hydroxysteroid dehydrogenase type 1, a modulator of glucocorticoids, suggests a potential role in IIH. Improved understanding of the complex interplay between adipose signaling factors such as adipokines, steroid hormones, and ICP regulation may be key to the understanding and future management of IIH. PMID:27186074

  10. Activation of pathways involved in HUVEC apoptosis and proliferation. Sex hormones agonist related. Effect of hormones on von Willebrand factor and ADAMTS 13 release

    OpenAIRE

    Powazniak, Yanina

    2008-01-01

    El VWF es una glicoproteína adhesiva, sintetizada en las CE y megacariocitos. Se sintetiza en forma monomérica, luego se organiza en dímeros y se multimeriza. El VWF media la adhesión de plaquetas al subendotelio vascular dañado y lel transporte del factor FVIII. La ADAMTS13, proteasa que cliva al VWF, pertenece a la familia de metaloproteasas ADAMTS, llamadas así por la combinación característica de una desintegrina y una metaloproteasa con motivos trombospondina tipo 1. La ADAMTS13 es sinte...

  11. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    International Nuclear Information System (INIS)

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

  12. Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

    Science.gov (United States)

    Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

    1996-04-01

    1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice

  13. Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21.

    Science.gov (United States)

    Iglesias, Pedro; Selgas, Rafael; Romero, Sara; Díez, Juan J

    2012-09-01

    Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as

  14. Prognostic factors of craniopharyngioma with special reference to autocrine/paracrine signaling: underestimated implication of growth hormone receptor.

    Science.gov (United States)

    Ogawa, Yoshikazu; Watanabe, Mika; Tominaga, Teiji

    2015-10-01

    Craniopharyngioma is a slow-growing tumor classified as benign, but tight adhesion and significant local infiltration to the vital structures are common. In spite of improvement of modern microsurgery techniques and precise anatomical understanding not few cases of this tumor recur, and long-term tumor control and maintenance of quality of life are sometimes difficult. However, very little is known about the effects of the molecular characters of craniopharyngioma on the prognosis. Ninety eight cases of craniopharyngioma surgically treated at the Department of Neurosurgery, Tohoku University Hospital and Kohnan Hospital from April 1996 to May 2014, 45 males and 53 females aged from 2 to 80 years (mean, 40.84 years) were retrospectively reviewed, and postoperative outcomes and the possible involvement of the autocrine/paracrine mechanism were investigated. The patients were followed up at intervals of 6 months to assess tumor recurrence, and clinical outcomes were correlated with the findings of immunohistochemical examinations used growth hormone receptor (GHR) and downstream hormones. The follow-up period ranged from 3 to 209 months. Hormone expression was examined in 88 patients, of which 46 specimens (52.3 %) showed high expression of GHR. The GHR high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.007). Simultaneous high expression of growth hormone (GH) and GHR was found in 33 specimens (37.5 %), and the high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.011). No other hormones showed statistically significant differences in outcomes. High expression of GHR is associated with shorter duration of postoperative stable disease in patients with craniopharyngioma. If the surgical specimens were craniopharyngiomas with high GHR expression, GH supplementation

  15. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.

    Directory of Open Access Journals (Sweden)

    Esther Roura

    Full Text Available In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC. However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3/carcinoma in situ (CIS and invasive cervical cancer (ICC.We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR, odds ratios (OR and corresponding 95% confidence intervals (CI. The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03. Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use. Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8. A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD was found in the nested case-control analysis (OR = 0.6. Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7.Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening

  16. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

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    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  17. Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans

    DEFF Research Database (Denmark)

    Heintz, Caroline; Doktor, Thomas K; Lanjuin, Anne

    2017-01-01

    via splicing factor 1 (SFA-1; the C. elegans homologue of SF1, also known as branchpoint binding protein, BBP). We show that SFA-1 is specifically required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also...... homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or subjected to dietary restriction, we find defects in global pre-mRNA splicing with age that are reduced by dietary restriction...

  18. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    Science.gov (United States)

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  19. Modulating factors in the expression of radiation-induced oncogenic transformation

    International Nuclear Information System (INIS)

    Hall, E.J.; Hei, T.K.

    1990-01-01

    Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing α-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene

  20. Is the renal kallikrein-kinin system a factor that modulates hypercalciuria?

    Directory of Open Access Journals (Sweden)

    Armando Luis Negri

    2017-01-01

    Full Text Available Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK. Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%. These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.

  1. Modulation of Tidal Channel Signatures on SAR Images Over Gyeonggi Bay in Relation to Environmental Factors

    Directory of Open Access Journals (Sweden)

    Tae-Sung Kim

    2018-04-01

    Full Text Available In this study, variations of radar backscatter features of the tidal channel in Gyeonggi Bay in the Eastern Yellow Sea were investigated using spaceborne synthetic aperture radar (SAR images. Consistent quasi-linear bright features appeared on the SAR images. Examining the detailed local bathymetry chart, we found that the features were co-located with the major axis of the tidal channel in the region. It was also shown that modulation of the radar backscatter features changed according to the environmental conditions at the time of imaging. For the statistical analysis, the bathymetric features over the tidal channel were extracted by an objective method. In terms of shape, the extracted features had higher variability in width than in length. The analysis of the variation in intensity with the coinciding bathymetric distribution confirmed that the quasi-linear bright features on the SAR images are fundamentally imprinted due to the surface current convergence and divergence caused by the bathymetry-induced tidal current variation. Furthermore, the contribution of environmental factors to the intensity modulation was quantitatively analyzed. A comparison of the variation in normalized radar cross section (NRCS with tidal current showed a positive correlation only with the perpendicular component of tidal current (r= 0.47. This implies that the modulation in intensity of the tidal channel signatures is mainly affected by the interaction with cross-current flow. On the other hand, the modulation of the NRCS over the tidal channel tended to be degraded as wind speed increased (r= −0.65. Considering the environmental circumstances in the study area, it can be inferred that the imaging capability of SAR for the detection of tidal channel signatures mainly relies on wind speed.

  2. Seasonal response of ghrelin, growth hormone, and insulin-like growth factor I in the free-ranging Florida manatee (Trichechus manatus latirostris)

    Science.gov (United States)

    Tighe, Rachel L; Bonde, Robert K.; Avery, Julie P.

    2016-01-01

    Seasonal changes in light, temperature, and food availability stimulate a physiological response in an animal. Seasonal adaptations are well studied in Arctic, Sub-Arctic, and hibernating mammals; however, limited studies have been conducted in sub-tropical species. The Florida manatee (Trichechus manatus latirostris), a sub-tropical marine mammal, forages less during colder temperatures and may rely on adipose stores for maintenance energy requirements. Metabolic hormones, growth hormone (GH), insulin-like growth factor (IGF)-I, and ghrelin influence growth rate, accretion of lean and adipose tissue. They have been shown to regulate seasonal changes in body composition. The objective of this research was to investigate manatee metabolic hormones in two seasons to determine if manatees exhibit seasonality and if these hormones are associated with seasonal changes in body composition. In addition, age related differences in these metabolic hormones were assessed in multiple age classes. Concentrations of GH, IGF-I, and ghrelin were quantified in adult manatee serum using heterologous radioimmunoassays. Samples were compared between short (winter) and long (summer) photoperiods (n = 22 male, 20 female) and by age class (adult, juvenile, and calf) in long photoperiods (n = 37). Short photoperiods tended to have reduced GH (p = 0.08), greater IGF-I (p = 0.01), and greater blubber depth (p = 0.03) compared with long photoperiods. No differences were observed in ghrelin (p = 0.66). Surprisingly, no age related differences were observed in IGF-I or ghrelin concentrations (p > 0.05). However, serum concentrations of GH tended (p = 0.07) to be greater in calves and juveniles compared with adults. Increased IGF-I, greater blubber thickness, and reduced GH during short photoperiod suggest a prioritization for adipose deposition. Whereas, increased GH, reduced blubber thickness, and decreased IGF-I in long photoperiod suggest prioritization of lean tissue

  3. Cavity Preparation/assembly Techniques and Impact on Q, Realistic Q - Factors in a Module, Review of Modules

    Energy Technology Data Exchange (ETDEWEB)

    Peter Kneisel

    2005-03-19

    This contribution summarizes the surface preparation procedures for niobium cavities presently used both in laboratory experiments and for modules, such as buffered chemical polishing (BCP), electropolishing (EP), high pressure ultrapure water rinsing (HPR), CO{sub 2} snow cleaning and high temperature heat treatments for hydrogen degassing or postpurification. The impact of surface treatments and the degree of cleanliness during assembly procedures on cavity performance (Q - value and accelerating gradient E{sub acc}) will be discussed. In addition, an attempt will be made to summarize the experiences made in module assemblies in different labs/projects such as DESY(TTF), Jlab (Upgrade) and SNS.

  4. Human Factors Support in the Design and Evaluation of the Reactor Protection System Cabinet Operator Module

    International Nuclear Information System (INIS)

    Lee, Hyun Chul; Lee, Jung Woon

    2005-01-01

    A Korean project group, KNICS, is developing a new digitalized reactor protection system (RPS) and the developed system will be packaged into a cabinet with several racks. The cabinet of the RPS is used for the RPS function testing and monitoring by maintenance operators and is equipped with a flat panel display (FPD) with a touch screen capability as a main user interface for the RPS operation. This paper describes the human factors activities involved in the development process of the RPS: conceptual design, design guidance, and evaluation. The activities include a functional requirements analysis and task analysis, user interface style guide for the RPS cabinet operator module (COM), and a human factors evaluation through an experiment and questionnaires

  5. Using Digital Images of the Zebra Finch Song System as a Tool to Teach Organizational Effects of Steroid Hormones: A Free Downloadable Module

    Science.gov (United States)

    Grisham, William; Schottler, Natalie A.; Beck McCauley, Lisa M.; Pham, Anh P.; Ruiz, Maureen L.; Fong, Michelle C.; Cui, Xinran

    2011-01-01

    Zebra finch song behavior is sexually dimorphic: males sing and females do not. The neural system underlying this behavior is sexually dimorphic, and this sex difference is easy to quantify. During development, the zebra finch song system can be altered by steroid hormones, specifically estradiol, which actually masculinizes it. Because of the…

  6. Structure of the Mr 140,000 growth hormone-dependent insulin-like growth factor binding protein complex: Determination by reconstitution and affinity-labeling

    International Nuclear Information System (INIS)

    Baxter, R.C.; Martin, J.L.

    1989-01-01

    To determine the structure of the high molecular weight, growth hormone-dependent complex between the insulin-like growth factors (IGF-I and IGF-II) and their binding proteins in human serum, we have reconstituted the complex from its purified component proteins and analyzed it by gel electrophoresis and autoradiography after covalent cross-linking. The proteins tested in reconstitution mixtures were an acid-labile Mr 84,000-86,000 glycoprotein doublet (alpha subunit), an acid-stable Mr 47,000-53,000 glycoprotein doublet with IGF-binding activity (BP-53 or beta subunit), and IGF-I or IGF-II (gamma subunit). In incubations containing any one of the three subunits 125I-labeled and the other two unlabeled, identical 125I-labeled alpha-beta-gamma complexes of Mr 140,000 were formed. Minor bands of Mr 120,000 and 90,000 were also seen, thought to represent a partially deglycosylated form of the alpha-beta-gamma complex, and an alpha-gamma complex arising as a cross-linking artifact. When serum samples from subjects of various growth hormone status were affinity-labeled with IGF-II tracer, a growth hormone-dependent Mr 140,000 band was seen, corresponding to the reconstituted alpha-beta-gamma complex. Other growth hormone-dependent labeled bands, of Mr 90,000 (corresponding to alpha-gamma), Mr 55,000-60,000 (corresponding to labeled beta-subunit doublet), and smaller bands of Mr 38,000, 28,000, and 23,000-25,000 (corresponding to labeled beta-subunit degradation products), were also seen in the affinity-labeled serum samples and in the complex reconstituted from pure proteins. All were immunoprecipitable with an anti-BP-53 antiserum. We conclude that the growth hormone-dependent Mr 140,000 IGF-binding protein complex in human serum has three components: the alpha (acid-labile) subunit, the beta (binding) subunit, and the gamma (growth factor) subunit

  7. Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

    Directory of Open Access Journals (Sweden)

    Kenneth R. Watterson

    2012-03-01

    Full Text Available Activation of mammalian target of rapamycin 1 (mTORC1 by nutrients, insulin and leptin leads to appetite suppression (anorexia. Contrastingly, increased AMP-activated protein kinase (AMPK activity by ghrelin promotes appetite (orexia. However, the interplay between these mechanisms remains poorly defined. The relationship between the anorexigenic hormones, insulin and leptin, and the orexigenic hormone, ghrelin, on mTORC1 signalling was examined using S6 kinase phosphorylation as a marker for changes in mTORC1 activity in mouse hypothalamic GT1-7 cells. Additionally, the contribution of AMPK and mTORC1 signalling in relation to insulin-, leptin- and ghrelin-driven alterations to mouse hypothalamic agouti-related protein (AgRP mRNA levels was examined. Insulin and leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K- and protein kinase B (PKB-dependent manner, compared to vehicle controls, whereas increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the anorexigenic hormones. Ghrelin mediates an AMPK-dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1-dependent manner. In conclusion, mTORC1 acts as an integration node in hypothalamic neurons for hormone-derived PI3K and AMPK signalling and mediates at least part of the assimilated output of anorexigenic and orexigenic hormone actions in the hypothalamus.

  8. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  9. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  10. Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

    Science.gov (United States)

    Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

    2016-01-01

    Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015

  11. Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy cows: I. Ovarian, conceptus, and growth hormone-insulin-like growth factor system responses.

    Science.gov (United States)

    Bilby, T R; Sozzi, A; Lopez, M M; Silvestre, F T; Ealy, A D; Staples, C R; Thatcher, W W

    2006-09-01

    The objective was to examine effects of bovine somatotropin (bST), pregnancy, and dietary fatty acids on reproductive responses in lactating dairy cows. Beginning at approximately 17 d in milk (DIM), a comparison was made of isoenergetic diets comprising supplementary lipids of whole cottonseed vs. calcium salts of fish oil enriched lipid (FO). Ovulation was synchronized in cows with a presynchronization plus Ovsynch protocol, and cows were inseminated artificially by appointment or not inseminated (d 0 = time of synchronized ovulation; 77 +/- 12 DIM). On d 0 and 11, cows received bST (500 mg) or no bST. All cows were slaughtered on d 17. Number of cows in each group was as follows: control diet had 5 bST-treated cyclic (bST-C), 5 non-bST-treated cyclic (no bST-C), 4 bST-treated pregnant (bST-P), and 5 non-bST-treated pregnant (no bST-P) cows; and cyclic cows fed FO diet had 4 bST-treated (bST-FO) and 5 non-bST-treated cyclic (no bST-FO-C) cows. Feeding FO increased milk production, number of class 1 follicles (2 to 5 mm), and decreased insulin during the period before d 0 compared with control-fed cows. The bST increased milk production, pregnancy rate [83% (5/6) vs. 40% (4/10)], conceptus length (45 vs. 34 cm), and interferon-tau in the uterine luminal flushings (9.4 vs. 5.3 microg) with no effect on interferon-tau mRNA concentration in the conceptus. Treatment with bST increased plasma growth hormone (GH) and insulin-like growth factor (IGF)-I. Among control-fed cows (cyclic and pregnant), bST decreased progesterone concentration in plasma. Cows fed FO had less plasma insulin than control-fed cyclic cows, and FO altered the plasma GH (bST-FO > bST-C) and IGF-I (bST-C > bST-FO-C) responses to bST injections. Endometrial IGF-I mRNA was reduced in pregnant cows and tended to decrease in those fed FO. The IGF-II mRNA was increased in the endometrium of pregnant and bST-treated cows fed the control diet. Cows fed FO had increased concentrations of IGF-II mRNA, when b

  12. Growth Hormone-Releasing Hormone in Diabetes

    Directory of Open Access Journals (Sweden)

    Leonid Evsey Fridlyand

    2016-10-01

    Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

  13. Foot length before and during insulin-like growth factor-I treatment of children with laron syndrome compared to human growth hormone treatment of children with isolated growth hormone deficiency.

    Science.gov (United States)

    Silbergeld, Aviva; Lilos, Pearl; Laron, Zvi

    2007-12-01

    To compare foot length deficits between patients with Laron syndrome (LS) (primary growth hormone [GH] insensitivity) and congenital isolated GH deficiency (IGHD) and their response to replacement therapy with insulin-like growth factor-I (IGF-I) and hGH, respectively. Data for the study were collected from the records of nine children with LS (3 M, 6 F) 7.8 +/- 4.8 years old (mean +/- SD), and nine children with IGHD (3 M, 6 F), 3.8 +/- 3.3 years old. Fifteen non-treated adult patients with LS were also included in the study. Measurements of foot length were recorded without treatment and monitored during 9 years of treatment in the children and in the untreated adult patients. For statistical analysis the non-parametric Mann-Whitney U test was used. With almost similar basal values in growth deficit and pre-treatment growth velocities, the achievements towards norms after 9 years of treatment were greater in the patients with IGHD than in the patients with LS: foot length reached -1.4 +/- 0.8 vs. -3.3 +/- 1.0 SDS (mean +/- SD), and body height -2.2 +/- 1.0 vs. -3.9 +/- 0.5 SDS. The difference between the two groups could be due to the initiation of replacement therapy in the patients with IGHD at a younger age. Adult foot size of untreated patients with LS is small but less retarded than the height deficit. Both IGF-I and hGH are potent growth stimulating hormones of linear growth and acrae as exemplified by foot growth.

  14. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

    Science.gov (United States)

    Stephenson, Kenna; Neuenschwander, Pierre F; Kurdowska, Anna K

    2013-01-01

    Menopause impacts 25 million women world wide each year, and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030. Menopause has been associated with symptoms of hot flashes, night sweats, dysphoric mood, sleep disturbance, and conditions of cardiovascular disease, depression, osteoporosis, osteoarthritis, depression, dementia, and frailty. Conventional hormone replacement therapy results in increased thrombotic events, and an increased risk of breast cancer and dementia as evidenced in large prospective clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women's Health Initiative. A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors. Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile, yet long-term studies of this treatment model are lacking. The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol, estradiol, progesterone, DHEA, and testosterone on cardiovascular biomarkers, hemostatic, inflammatory, immune signaling factors; quality-of-life measures; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care. A prospective, cohort, closed-label study received approval from the Human Subjects Committee. Recruitment from outpatient clinics at an academic medical center and the community at large resulted in three hundred women giving signed consent. Seventy-five women who met strict inclusion/exclusion criteria were enrolled. Baseline hormone evaluation was performed along with baseline experimental measures. Following this, women received compounded transdermal bioidentical hormone therapy of BiEst (80%Estriol/20%Estradiol), and

  15. Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle

    OpenAIRE

    Becú-Villalobos, Damasia; García-Tornadú, Isabel; Shroeder, Guillermo; Salado, Eloy E.; Gagliostro, Gerardo; Delavaud, Carole; Chilliard, Yves; Lacau-Mengido, Isabel M.

    2007-01-01

    We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil s...

  16. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum

    DEFF Research Database (Denmark)

    Møller, U K; við Streym, Susanna; Mosekilde, L

    2013-01-01

    physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. METHODS: We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16...... and 36 weeks postpartum. The controls were followed in parallel. RESULTS: P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (p... resorption and formation rose and fall, respectively (p

  17. Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Zhong, Guo-Chao; Liu, Yan; Chen, Nan; Hao, Fa-Bao; Wang, Kang; Cheng, Jia-Hao; Gong, Jian-Ping; Ding, Xiong

    2016-12-01

    A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case-control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases ≥100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (P non-linearity  Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings

  18. Differential growth factor induction and modulation of human gastric epithelial regeneration

    International Nuclear Information System (INIS)

    Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel

    2005-01-01

    While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGFα, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFβ pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFα exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGFα and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair

  19. Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice.

    Science.gov (United States)

    Xing, Weirong; Govoni, Kristen E; Donahue, Leah Rae; Kesavan, Chandrasekhar; Wergedal, Jon; Long, Carlin; Bassett, J H Duncan; Gogakos, Apostolos; Wojcicka, Anna; Williams, Graham R; Mohan, Subburaman

    2012-05-01

    Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) (Tshr(-/-) and Duox2(-/-)), growth hormone (GH) (Ghrhr(lit/lit)), or both (Tshr(-/-); Ghrhr(lit/lit)), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition. Copyright © 2012 American Society for Bone and Mineral Research.

  20. Rearing Mozambique tilapia in tidally-changing salinities: Effects on growth and the growth hormone/insulin-like growth factor I axis.

    Science.gov (United States)

    Moorman, Benjamin P; Yamaguchi, Yoko; Lerner, Darren T; Grau, E Gordon; Seale, Andre P

    2016-08-01

    The growth hormone (GH)/insulin-like growth factor (IGF) axis plays a central role in the regulation of growth in teleosts and has been shown to be affected by acclimation salinity. This study was aimed at characterizing the effects of rearing tilapia, Oreochromis mossambicus, in a tidally-changing salinity on the GH/IGF axis and growth. Tilapia were raised in fresh water (FW), seawater (SW), or in a tidally-changing environment, in which salinity is switched between FW (TF) and SW (TS) every 6h, for 4months. Growth was measured over all time points recorded and fish reared in a tidally-changing environment grew significantly faster than other groups. The levels of circulating growth hormone (GH), insulin-like growth factor I (IGF-I), pituitary GH mRNA, gene expression of IGF-I, IGF-II, and growth hormone receptor 2 (GHR) in the muscle and liver were also determined. Plasma IGF-I was higher in FW and TS than in SW and TF tilapia. Pituitary GH mRNA was higher in TF and TS than in FW and SW tilapia. Gene expression of IGF-I in the liver and of GHR in both the muscle and liver changed between TF and TS fish. Fish growth was positively correlated with GH mRNA expression in the pituitary, and GHR mRNA expression in muscle and liver tissues. Our study indicates that rearing fish under tidally-changing salinities elicits a distinct pattern of endocrine regulation from that observed in fish reared in steady-state conditions, and may provide a new approach to increase tilapia growth rate and study the regulation of growth in euryhaline fish. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Analysis of Factors Influencing the Development of Xerostomia during Intensity-Modulated Radiotherapy

    Science.gov (United States)

    Randall, Ken; Stevens, Jason; Yepes, Juan Fernando; Randall, Marcus E.; Kudrimoti, Mahesh; Feddock, Jonathan; Xi, Jing; Kryscio, Richard J.; Miller, Craig S.

    2013-01-01

    OBJECTIVES Factors influencing xerostomia during intensity-modulated radiation therapy (IMRT) were assessed. METHODS A 6-week study of 32 head and neck cancer (HNC) patients was performed. Subjects completed the Xerostomia Inventory (XI) and provided stimulated saliva (SS) at baseline, week two and at end of IMRT. Influence of SS flow rate (SSFR), calcium and mucin 5b (MUC5b) concentrations and radiation dose on xerostomia was determined. RESULTS HNC subjects experienced mean SSFR decline of 36% by visit two (N=27; p=0.012) and 57% by visit three (N=20; p=0.0004), Concentrations of calcium and MUC5b increased, but not significantly during IMRT (p>0.05). Xerostomia correlated most with decreasing salivary flow rate as determined by Spearman correlations (pxerostomia. PMID:23523462

  2. Modulation of radiation effects in tissues by keratinocyte growth factor (KGF)

    International Nuclear Information System (INIS)

    Doerr, W.; Lacmann, A.; Noack, R.; Spekl, K.

    2000-01-01

    Keratinocyte Growth Factor (KGF) is a member of the fibroblast growth factor family. KGF is produced by mesenchymal cells, predominantly fibroblasts; target cells are epithelial cells in a variety of tissues. Hence, KGF is a mediator of the mesenchymal-epithelial communication and a regulator of tissue homeostasis in epithelia. Systemic administration of KGF in animal models induces stimulation of proliferation and modulation of migration and differentiation processes in squamous epithelia. This results in a transient increase in cell numbers and epithelial thickness. Radiation exposure of epithelia causes an imbalance between cell production and cell loss, which in consequence causes progressive cell depletion and eventually complete denudation. Systemic application of KGF reduces the radiation-induced cell loss. This effect is most pronounced when KGF is given after the radiation exposure. With regard to epithelial radiation tolerance, KGF-application in animal models results in a significant increase, by a factor of 1.7-2.3, in the doses required to induce epithelial ulceration as a clinically most relevant endpoint. After exposure with a given dose, this translates into a significant reduction of the clinical manifestation of the acute radiation sequelae. This effect is accompanied by a modification of the time course of the response. In conclusion, although the mechanisms underlying the protective efficacy remain unclear, KGF may represent an effective approach for amelioration of radiation effects in oral, gastrointestinal and cutaneous epithelia. Results from a clinical pilot study indicate that KGF is well tolerated and effective in humans. (orig.) [de

  3. pH modulates the binding of early growth response protein 1 transcription factor to DNA.

    Science.gov (United States)

    Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

    2013-08-01

    The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

  4. pH Modulates the Binding of EGR1 Transcription Factor to DNA

    Science.gov (United States)

    Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

    2013-01-01

    EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

  5. HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wen-Tsung Huang

    2017-12-01

    Full Text Available Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+ breast cancer patients. Even though dysregulations of histone deacetylases (HDACs are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

  6. Control of leptin by metabolic state and its regulatory interactions with pituitary growth hormone and hepatic growth hormone receptors and insulin like growth factors in the tilapia (Oreochromis mossambicus).

    Science.gov (United States)

    Douros, Jonathan D; Baltzegar, David A; Mankiewicz, Jamie; Taylor, Jordan; Yamaguchi, Yoko; Lerner, Darren T; Seale, Andre P; Grau, E Gordon; Breves, Jason P; Borski, Russell J

    2017-01-01

    Leptin is an important cytokine for regulating energy homeostasis, however, relatively little is known about its function and control in teleost fishes or other ectotherms, particularly with regard to interactions with the growth hormone (GH)/insulin-like growth factors (IGFs) growth regulatory axis. Here we assessed the regulation of LepA, the dominant paralog in tilapia (Oreochromis mossambicus) and other teleosts under altered nutritional state, and evaluated how LepA might alter pituitary growth hormone (GH) and hepatic insulin-like growth factors (IGFs) that are known to be disparately regulated by metabolic state. Circulating LepA, and lepa and lepr gene expression increased after 3-weeks fasting and declined to control levels 10days following refeeding. This pattern of leptin regulation by metabolic state is similar to that previously observed for pituitary GH and opposite that of hepatic GHR and/or IGF dynamics in tilapia and other fishes. We therefore evaluated if LepA might differentially regulate pituitary GH, and hepatic GH receptors (GHRs) and IGFs. Recombinant tilapia LepA (rtLepA) increased hepatic gene expression of igf-1, igf-2, ghr-1, and ghr-2 from isolated hepatocytes following 24h incubation. Intraperitoneal rtLepA injection, on the other hand, stimulated hepatic igf-1, but had little effect on hepatic igf-2, ghr1, or ghr2 mRNA abundance. LepA suppressed GH accumulation and gh mRNA in pituitaries in vitro, but had no effect on GH release. We next sought to test if abolition of pituitary GH via hypophysectomy (Hx) affects the expression of hepatic lepa and lepr. Hypophysectomy significantly increases hepatic lepa mRNA abundance, while GH replacement in Hx fish restores lepa mRNA levels to that of sham controls. Leptin receptor (lepr) mRNA was unchanged by Hx. In in vitro hepatocyte incubations, GH inhibits lepa and lepr mRNA expression at low concentrations, while higher concentration stimulates lepa expression. Taken together, these findings

  7. Social and environmental factors modulate leucocyte profiles in free-living Greylag geese (Anser anser

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    Didone Frigerio

    2017-01-01

    Full Text Available Background Blood parameters such as haematocrit or leucocyte counts are indicators of immune status and health, which can be affected, in a complex way, by exogenous as well as endogenous factors. Additionally, social context is known to be among the most potent stressors in group living individuals, therefore potentially influencing haematological parameters. However, with few exceptions, this potential causal relationship received only moderate scientific attention. Methods In a free-living and individually marked population of the highly social and long-lived Greylag goose, Anser anser, we relate variation in haematocrit (HCT, heterophils to lymphocytes ratio (H/L and blood leucocyte counts to the following factors: intrinsic (sex, age, raising condition, i.e. goose- or hand-raised, social (pair-bond status, pair-bond duration and parental experience and environmental (biologically relevant periods, ambient temperature factors. Blood samples were collected repeatedly from a total of 105 focal birds during three biologically relevant seasons (winter flock, mating season, summer. Results We found significant relationships between haematological parameters and social as well as environmental factors. During the mating season, unpaired individuals had higher HCT compared to paired and family individuals and this pattern reversed in fall. Similarly, H/L ratio was positively related to pair-bond status in a seasonally dependent way, with highest values during mating and successful pairs had higher H/L ratio than unsuccessful ones. Also, absolute number of leucocytes tended to vary depending on raising condition in a seasonally dependent way. Discussion Haematology bears a great potential in ecological and behavioural studies on wild vertebrates. In sum, we found that HTC, H/L ratio and absolute number of leucocytes are modulated by social factors and conclude that they may be considered valid indicators of individual stress load.

  8. The rate and factors associated with non-adherence to surgery, chemotherapy, radiotherapy and hormonal therapy among breast cancer patients attending public hospitals in Malaysia

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    Nur Aishah Taib

    2017-12-01

    Full Text Available Background: The role of breast cancer treatments in reducing recurrence and death has been established. However, the treatments side effects greatly impact on quality of life and little is known about the non-adherence rates. The purpose of this study was to determine the non-adherence rates to surgery, chemotherapy, radiotherapy and hormonal therapy, and factors that affect it in public hospitals in Malaysia. Methods: A multicentre cross-sectional study was conducted in six public hospitals involving all newly diagnosed breast cancer patients in 2012. Data were collected through medical record reviews and interview by using structured questionnaire. Non-adherence was categorized as any breast cancer patients refusing or discontinuing any treatment due to non-medical reasons. Univariable logistic regression and multiple logistic regressions were used for analysis. Results: A total of 340 breast cancer patients were included in the study. The proportion for non-adherence to surgery, chemotherapy, radiotherapy and hormonal therapy were 14%, 30.1%, 33.3% and 36.3% respectively. Factors associated with non-adherence to surgery were localities involving Kuala Lumpur (2 (OR: 3.41, Johor (OR: 8.38 and Kelantan (OR: 6.32, and those required mastectomy (OR: 5.66. No factors were found to be associated with non-adherence to chemotherapy, radiotherapy and hormonal therapy. These three treatment modalities were then combined as oncology therapy and the only independent factor associated with non-adherence to oncology therapy was Perak locality (OR: 1.42. Conclusion: Non-adherence to breast cancer treatments was high among breast cancer patients at public hospitals in Malaysia. Factors influencing non-adherence were locations and mastectomy implicating of socio-culture, body image issues, psychological disturbance and treatment navigation. Community educational programs focusing on correcting misconceptions, treatment outcomes and treatments’ side effects

  9. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.

    Science.gov (United States)

    Burgess, W; Liu, Q; Zhou, J; Tang, Q; Ozawa, A; VanHoy, R; Arkins, S; Dantzer, R; Kelley, K W

    1999-01-01

    Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of

  10. Hypothesis: Genetic and epigenetic risk factors interact to modulate vulnerability and resilience to FASD

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    Elif eTunc-Ozcan

    2014-08-01

    Full Text Available Fetal alcohol spectrum disorder (FASD presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus’ vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or ‘exceptions’ to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual’s symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal versus paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring’s vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond.

  11. Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary.

    Science.gov (United States)

    Liu, Y; Lin, L; Zarnegar, R

    1994-09-01

    Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.

  12. Ontogeny and nutritional programming of the hepatic growth hormone-insulin-like growth factor-prolactin axis in the sheep.

    Science.gov (United States)

    Hyatt, Melanie A; Budge, Helen; Walker, David; Stephenson, Terence; Symonds, Michael E

    2007-10-01

    The liver is an important metabolic and endocrine organ in the fetus, but the extent to which its hormone receptor sensitivity is developmentally regulated in early life is not fully established. Therefore, we examined developmental changes in mRNA abundance for the GH receptor (GHR) and prolactin receptor (PRLR) plus IGF-I and -II and their receptors. Fetal and postnatal sheep were sampled at either 80 or 140 d gestation, 1 or 30 d, or 6 months of age. The effect of maternal nutrient restriction between early gestation to midgestation (i.e. 28-80 d gestation, the time of early liver growth) on gene expression was also examined in the fetus and juvenile offspring. Gene expression for the GHR, PRLR, and IGF-I receptor increased through gestation peaking at birth, whereas IGF-I was maximal near to term. In contrast, IGF-II mRNA decreased between midgestation and late gestation to increase after birth, whereas IGF-II receptor remained unchanged. A substantial decline in mRNA abundance for GHR, PRLR, and IGF-I receptor then occurred up to 6 months. Maternal nutrient restriction reduced GHR and IGF-II receptor mRNA abundance in the fetus, but caused a precocious increase in the PRLR. Gene expression for IGF-I and -II were increased in juvenile offspring born to nutrient-restricted mothers. In conclusion, there are marked differences in the ontogeny and nutritional programming of specific hormones and their receptors involved in hepatic growth and development in the fetus. These could contribute to changes in liver function during adult life.

  13. Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases

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    Marta Pajares

    2017-04-01

    Full Text Available Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2-like 2. NRF2 has been classically considered as the master regulator of the antioxidant cell response, although it is currently emerging as a key component of the transduction machinery to maintain proteostasis. As we will discuss, NRF2 could be envisioned as a hub that compiles emergency signals derived from misfolded protein accumulation in order to build a coordinated and perdurable transcriptional response. This is achieved by functions of NRF2 related to the control of genes involved in the maintenance of the endoplasmic reticulum physiology, the proteasome and autophagy.

  14. Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist.

    Science.gov (United States)

    Yun, Bo Seong; Seong, Seok Ju; Cha, Dong Hyun; Kim, Ji Yeon; Kim, Mi-La; Shim, Jeong Yun; Park, Ji Eun

    2015-08-01

    To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein. Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot. A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein. Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Gap junction modulation by extracellular signaling molecules: the thymus model

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    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  16. The role of releasing hormones in the diagnosis of hypopituitarism ...

    African Journals Online (AJOL)

    Luteinising hormone-releasing factor and thyrotrophinreleasing factor were used in conjunction with the insulin tolerance test in 9 patients with known or suspected panhypopituitarism. It appears that growth hormone and luteinising hormone fail early in panhypopituitarism. Cortisol and thyroid-stimulating hormone ...

  17. Identification and expression analysis of WRKY transcription factor genes in canola (Brassica napus L. in response to fungal pathogens and hormone treatments

    Directory of Open Access Journals (Sweden)

    Deyholos Michael K

    2009-06-01

    Full Text Available Abstract Background Members of plant WRKY transcription factor families are widely implicated in defense responses and various other physiological processes. For canola (Brassica napus L., no WRKY genes have been described in detail. Because of the economic importance of this crop, and its evolutionary relationship to Arabidopsis thaliana, we sought to characterize a subset of canola WRKY genes in the context of pathogen and hormone responses. Results In this study, we identified 46 WRKY genes from canola by mining the expressed sequence tag (EST database and cloned cDNA sequences of 38 BnWRKYs. A phylogenetic tree was constructed using the conserved WRKY domain amino acid sequences, which demonstrated that BnWRKYs can be divided into three major groups. We further compared BnWRKYs to the 72 WRKY genes from Arabidopsis and 91 WRKY from rice, and we identified 46 presumptive orthologs of AtWRKY genes. We examined the subcellular localization of four BnWRKY proteins using green fluorescent protein (GFP and we observed the fluorescent green signals in the nucleus only. The responses of 16 selected BnWRKY genes to two fungal pathogens, Sclerotinia sclerotiorum and Alternaria brassicae, were analyzed by quantitative real time-PCR (qRT-PCR. Transcript abundance of 13 BnWRKY genes changed significantly following pathogen challenge: transcripts of 10 WRKYs increased in abundance, two WRKY transcripts decreased after infection, and one decreased at 12 h post-infection but increased later on (72 h. We also observed that transcript abundance of 13/16 BnWRKY genes was responsive to one or more hormones, including abscisic acid (ABA, and cytokinin (6-benzylaminopurine, BAP and the defense signaling molecules jasmonic acid (JA, salicylic acid (SA, and ethylene (ET. We compared these transcript expression patterns to those previously described for presumptive orthologs of these genes in Arabidopsis and rice, and observed both similarities and differences in

  18. Hormonal control of euryhalinity

    Science.gov (United States)

    Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  19. Significance of determination of female sex hormones (E2, LH, FSH), insulin-like growth factor I (IGF-I) and leptin in girls with precocious puberty

    International Nuclear Information System (INIS)

    Huang Jianrong

    2004-01-01

    Objective: To investigate the diagnostic value of determination of serum levels of estradiol (E 2 ), luteinizing hormone (LH) and follicle stimulating hormone (FSH), insulin-like growth factor (IGF-I) and leptin in girls with idiopathic central precocious puberty (ICPP). Methods: Serum E 2 , LH, FSH, IGF-I (with chemiluminescence immunoassay) and leptin (with RIA) levels were determined in 35 girls with early development of breast as the sign of precocious puberty, of which, 15 was considered to be of the ICPP group and 20 of simple premature thelarche group (SPT). Criteria of diagnosis for ICPP were: peak LH value>12IU/L and LH/FSH>1 after GnRH stimulating test. Results: Serum E 2 , LH, FSH, IGF-I leptin levels in girls with ICPP were significantly higher than those in the girls with SPT (P 0.2 as the cut-off value for diagnosis of ICPP there would still be a positive rate of 86.6% suggesting that the diagnostic criteria might be set lower. Serum IGF-I levels were positively correlated to those of E 2 (r=0.47, P 2 and IGF-I. Conclusion: Determinations of serum E 2 , LH, FHS, IGF-I and leptin levels were helpful for the early diagnosis of ICPP. (author)

  20. Juvenile hormone counteracts the bHLH-PAS transcription factors MET and GCE to prevent caspase-dependent programmed cell death in Drosophila.

    Science.gov (United States)

    Liu, Ying; Sheng, Zhentao; Liu, Hanhan; Wen, Di; He, Qianyu; Wang, Sheng; Shao, Wei; Jiang, Rong-Jing; An, Shiheng; Sun, Yaning; Bendena, William G; Wang, Jian; Gilbert, Lawrence I; Wilson, Thomas G; Song, Qisheng; Li, Sheng

    2009-06-01

    Juvenile hormone (JH) regulates many developmental and physiological events in insects, but its molecular mechanism remains conjectural. Here we report that genetic ablation of the corpus allatum cells of the Drosophila ring gland (the JH source) resulted in JH deficiency, pupal lethality and precocious and enhanced programmed cell death (PCD) of the larval fat body. In the fat body of the JH-deficient animals, Dronc and Drice, two caspase genes that are crucial for PCD induced by the molting hormone 20-hydroxyecdysone (20E), were significantly upregulated. These results demonstrated that JH antagonizes 20E-induced PCD by restricting the mRNA levels of Dronc and Drice. The antagonizing effect of JH on 20E-induced PCD in the fat body was further confirmed in the JH-deficient animals by 20E treatment and RNA interference of the 20E receptor EcR. Moreover, MET and GCE, the bHLH-PAS transcription factors involved in JH action, were shown to induce PCD by upregulating Dronc and Drice. In the Met- and gce-deficient animals, Dronc and Drice were downregulated, whereas in the Met-overexpression fat body, Dronc and Drice were significantly upregulated leading to precocious and enhanced PCD, and this upregulation could be suppressed by application of the JH agonist methoprene. For the first time, we demonstrate that JH counteracts MET and GCE to prevent caspase-dependent PCD in controlling fat body remodeling and larval-pupal metamorphosis in Drosophila.

  1. The interaction between menstrual cycle, Tumour Necrosis Factor alpha receptors and sex hormones in healthy non-obese women – results from an observational study

    Directory of Open Access Journals (Sweden)

    Paweł Rzymski

    2014-09-01

    Full Text Available There is growing evidence that TNF-alpha and its two receptors play an important role in hormonal regulation, metabolism, inflammation and cancer. The biological effects of TNF-alpha are mediated by two receptors, p55 and p75. The aim of this study was to analyze serum concentrations of p55 and p75 and hormonal status in healthy women during the normal menstrual cycle. Eight women aged 20–22 with regular menstrual cycles were scheduled for examination on 3[sup]rd[/sup] , 8[sup]th[/sup] , 14[sup]th[/sup] and 25[sup]th [/sup] day of their menstrual cycle. We only observed a positive correlation of p75 subunit with prolactin level (correlation coefficient 0.417; p=0.0116 and negative correlation with insulin level (correlation coefficient -0.35; p=0.032 and HOMA[sub]IR[/sub] insulin resistance index correlation coefficient 0.39; p=0.0185. Furthermore, a negative correlation of p55/p75 ratio with prolactin (correlation coefficient -0.42; p=0.0101 and a positive correlations of p55/p75 ratio with insulin level (correlation coefficient 0.43; p=0.008 and HOMA[sub]IR[/sub] insulin resistance factor correlation coefficient 0.45; p=0.0065 were found.

  2. Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)

    1984-01-01

    The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

  3. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study.

    Science.gov (United States)

    Møller, U K; Streym, S; Mosekilde, L; Heickendorff, L; Flyvbjerg, A; Frystyk, J; Jensen, L T; Rejnmark, L

    2013-04-01

    Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactation We describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel. P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (phormone (P-PTH) and calcitonin decreased (pgrowth factor I (IGF-I) was suppressed (pbone resorption and formation rose and fall, respectively (pbone formation markers increased in association with IGF-I changes (pbone turnover markers were associated with lactation status (pbone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.

  4. Thyroid Hormone, Cancer, and Apoptosis.

    Science.gov (United States)

    Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

    2016-06-13

    Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  5. Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

    Science.gov (United States)

    Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

    2009-07-01

    We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

  6. Effects of aerobic exercise training on serum sex hormone binding globulin, body fat index, and metabolic syndrome factors in obese postmenopausal women.

    Science.gov (United States)

    Kim, Jong-Won; Kim, Do-Yeon

    2012-12-01

    The percentage of obese postmenopausal women with metabolic syndrome is rising, and physical factors associated with the metabolic syndrome prevalence or incidence are also rising, including high body mass index (BMI), visceral fat area (VFA), low plasma sex hormone-binding globulin (SHBG) levels, and low cardiorespiratory fitness. Therefore, we investigated the influence of aerobic exercise on SHBG, body fat index (BFI), and metabolic syndrome factors in obese postmenopausal Korean women. Thirty healthy postmenopausal, women aged 53.46 ± 2.4 years and with over 32% body fat, were randomly assigned to an aerobic exercise group (EX; n=15) or to a "nonexercise" control (Con; n=15) group. The primary outcome measurements were serum SHBG, lipid profiles, insulin levels, and metabolic syndrome factors. Secondary outcome measurements were body composition, VFA, blood pressure (BP), and homeostasis model assessment of insulin resistance (HOMA-IR). Posttraining body weight and BFI (Pmetabolic syndrome factors (Pexercise group but not in the control group. SHBG levels also showed a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) and significant negative correlations withglucose, diastolic blood pressure, fat mass, BMI, and percent body fat (Pexercise improves body composition, SHBG, insulin levels, and metabolic syndrome factors. These findings suggest that in obesepostmenopausal Korean women, 16 weeks of aerobic exercise is effective for preventing the metabolic syndrome caused by obesity.

  7. Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone.

    Science.gov (United States)

    Murata, J; Ayukawa, K; Ogasawara, M; Watanabe, H; Saiki, I

    1999-03-15

    We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).

  8. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  9. Environmental and hormonal factors in seasonal breeding in free-living male Indian rose-ringed parakeets (Psittacula krameri).

    Science.gov (United States)

    Krishnaprasadan, T N; Kotak, V C; Sharp, P J; Schmedemann, R; Haase, E

    1988-12-01

    Seasonal changes in testicular activity, plasma luteinizing hormone (LH), estradiol (E2), testosterone (T), and 5 alpha-dihydrotestosterone (5 alpha-DHT) were related to pair bond formation, nest building, nest defense, and parental behavior in free-living Indian rose-ringed parakeets (Psittacula krameri) in northwest India. Spermatozoa production occurred between January and March when daylengths were short (10-12 hr) and ambient temperature was seasonally low (8-20 degrees C). At other times of the year the testes were regressed. Plasma LH levels increased during the prebreeding period (September-December) when the birds were forming pairs and selecting or defending nest sites. Plasma LH levels increased further between January and March and decreased to seasonal low values during the post breeding period between April and June when the birds were caring for young. Concentrations of plasma androgens and estrogens were similar during the prebreeding and postbreeding phases of the breeding cycle. During the breeding period, the ratios between plasma 5 alpha-DHT and testosterone and between plasma estradiol and testosterone increased. It is proposed that the absence of marked seasonal changes in plasma steroid levels is related to nest defense behavior which occurs during the prebreeding, breeding, and postbreeding phases of the breeding cycle. Winter breeding makes it possible for the parakeets to avoid competition with other birds for nesting sites, to avoid fledging young during the monsoon period, and to take advantage of the winter pea crop which provides the female with extra nutrients for egg production.

  10. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

    Directory of Open Access Journals (Sweden)

    Aline Bertin

    2015-11-01

    Full Text Available In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H and from sham embryos (C that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment.

  11. Ovarian sex hormones modulate compulsive, affective and cognitive functions in a non-induced mouse model of obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Swarup Mitra

    2016-11-01

    Full Text Available There is currently a lack of understanding how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female OCD patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX, which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After seven days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2 or progesterone (P4 could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background.

  12. High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

    Science.gov (United States)

    Prodam, Flavia; Ricotti, Roberta; Agarla, Valentina; Parlamento, Silvia; Genoni, Giulia; Balossini, Caterina; Walker, Gillian Elisabeth; Aimaretti, Gianluca; Bona, Gianni; Bellone, Simonetta

    2013-02-20

    The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia

  13. Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts.

    Science.gov (United States)

    Massicotte, Frédéric; Fernandes, Julio Cesar; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lajeunesse, Daniel

    2006-03-01

    Human osteoarthritis (OA) is characterized by cartilage loss, bone sclerosis, osteophyte formation and inflammation of the synovial membrane. We previously reported that OA osteoblasts (Ob) show abnormal phenotypic characteristics possibly responsible for bone sclerosis and that two subgroups of OA patients can be identified by low or high endogenous production of prostaglandin E2 (PGE2) by OA Ob. Here, we determined that the elevated PGE2 levels in the high OA subgroup were linked with enhanced cyclooxygenase-2 (COX-2) protein levels compared to normal and low OA Ob. A linear relationship was observed between endogenous PGE2 levels and insulin-like growth factor 1 (IGF-1) levels in OA Ob. As parathyroid hormone (PTH) and PGE2 are known stimulators of IGF-1 production in Ob, we next evaluated their effect in OA Ob. Both subgroups increased their IGF-1 production similarly in response to PGE2, while the high OA subgroup showed a blunted response to PTH compared to the low OA group. Conversely, only the high OA group showed a significant inhibition of IGF-1 production when PGE2 synthesis was reduced with Naproxen, a non-steroidal antiinflammatory drug (NSAID) that inhibits cyclooxygenases (COX). The PGE2-dependent stimulation of IGF-1 synthesis was due in part to the cAMP/protein kinase A pathway since both the direct inhibition of this pathway with H-89 and the inhibition of EP2 or EP4 receptors, linked to cAMP production, reduced IGF-1 synthesis. The production of the most abundant IGF-1 binding proteins (IGFBPs) in bone tissue, IGFBP-3, -4, and -5, was lower in OA compared to normal Ob independently of the OA group. Under basal condition, OA Ob expressed similar IGF-1 mRNA to normal Ob; however, PGE2 stimulated IGF-1 mRNA expression more in OA than normal Ob. These data suggest that increased IGF-1 levels correlate with elevated endogenous PGE2 levels in OA Ob and that higher IGF-1 levels in OA Ob could be important for bone sclerosis in OA.

  14. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    NARCIS (Netherlands)

    Kroening, Sven; Neubauer, Emily; Wullich, Bernd; Aten, Jan; Goppelt-Struebe, Margarete

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009;

  15. Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins.

    Science.gov (United States)

    Sun, Hongliu; Nelms, Brian L; Sleiman, Sama F; Chamberlin, Helen M; Hanna-Rose, Wendy

    2007-10-01

    The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.

  16. The Effect of Recombinant Growth Hormone Treatment in Children with Idiopathic Short Stature and Low Insulin-Like Growth Factor-1 Levels.

    Science.gov (United States)

    Şıklar, Zeynep; Kocaay, Pınar; Çamtosun, Emine; İsakoca, Mehmet; Hacıhamdioğlu, Bülent; Savaş Erdeve, Şenay; Berberoğlu, Merih

    2015-12-01

    Idiopathic short stature (ISS) constitutes a heterogeneous group of short stature which is not associated with an endocrine or other identifiable cause. Some ISS patients may have varying degrees of insulin-like growth factor-1 (IGF-1) deficiency. Recombinant growth hormone (rGH) treatment has been used by some authors with variable results. Reports on long-term rGH treatment are limited. In this study, 21 slowly growing, non-GH-deficient ISS children who received rGH treatment for 3.62±0.92 years were evaluated at the end of a 5.42±1.67-year follow-up period. The study group included patients with low IGF-1 levels who also responded well to an IGF generation test. The patients were divided into two groups as good responders [height increment >1 standard deviation (SD)] and poor responders (height increment deficit and almost 40% of patients may reach their target height.

  17. Modulation of Myostatin/Hepatocyte Growth Factor Balance by Different Hemodialysis Modalities

    Directory of Open Access Journals (Sweden)

    Pasquale Esposito

    2017-01-01

    Full Text Available Background. In this study we investigated the relevance of myostatin and Hepatocyte Growth Factor (HGF in patients undergoing hemodialysis HD and the influence of different HD modalities on their levels. Methods. We performed a prospective crossover study in which HD patients were randomized to undergo 3-month treatment periods with bicarbonate hemodialysis (BHD followed by online hemodiafiltration (HDF. Clinical data, laboratory parameters, and myostatin and HGF serum levels were collected and compared. Results. Ten patients and six controls (C were evaluated. In any experimental condition myostatin and HGF levels were higher in HD than in C. At enrollment and after BHD there were not significant correlations, whereas at the end of the HDF treatment period myostatin and HGF were inversely correlated (r  -0.65, p<0.05, myostatin serum levels inversely correlated with transferrin (r  -0.73, p<0.05, and HGF levels that resulted positively correlated with BMI (r 0.67, p<0.05. Moving from BHD to HDF, clinical and laboratory parameters were unchanged, as well as serum HGF, whereas myostatin levels significantly decreased (6.3 ± 4.1 versus 4.3 ± 3.1 ng/ml, p<0.05. Conclusions. Modulation of myostatin levels and myostatin/HGF balance by the use of different HD modalities might represent a novel approach to the prevention and treatment of HD-related muscle wasting syndrome.

  18. Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone

    Directory of Open Access Journals (Sweden)

    Senthil R. Kumar

    2018-01-01

    Full Text Available The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl-homoserine lactone (C12-HSL on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA cells (DU145 and LNCaP and prostate small cell neuroendocrine carcinoma (SCNC PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1 were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.

  19. Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jingshan Zhao

    Full Text Available The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL, a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF signaling and angiogenesis in endothelial cells (ECs. We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

  20. The Prevalence of Premenstrual Dysphoric Disorder and Its Modulation by Lifestyle and Psychological Factors in High School Students

    OpenAIRE

    Hapsari, Elsi Dwi; Mantani, Yuria; Matsuo, Hiroya

    2006-01-01

    The purposes of this study were to investigate the prevalence of PMDD in Japanese adolescent girls and identify PMDD modulation by lifestyle and psychological factors and compared the result with those in PMS. Self-reported questionnaires were delivered to 675 high school students in Kobe City from June to July 2004. Items of questionnaires have included student's background, menstruation, lifestyle factors and health difficulties. Diagnosis criteria of PMS from Mortola et al. and diagnosis o...

  1. AP2/EREBP transcription factors are part of gene regulatory networks and integrate metabolic, hormonal and environmental signals in stress acclimation and retrograde signalling.

    Science.gov (United States)

    Dietz, Karl-Josef; Vogel, Marc Oliver; Viehhauser, Andrea

    2010-09-01

    To optimize acclimation responses to environmental growth conditions, plants integrate and weigh a diversity of input signals. Signal integration within the signalling networks occurs at different sites including the level of transcription factor activation. Accumulating evidence assigns a major and diversified role in environmental signal integration to the family of APETALA 2/ethylene response element binding protein (AP2/EREBP) transcription factors. Presently, the Plant Transcription Factor Database 3.0 assigns 147 gene loci to this family in Arabidopsis thaliana, 200 in Populus trichocarpa and 163 in Oryza sativa subsp. japonica as compared to 13 to 14 in unicellular algae ( http://plntfdb.bio.uni-potsdam.de/v3.0/ ). AP2/EREBP transcription factors have been implicated in hormone, sugar and redox signalling in context of abiotic stresses such as cold and drought. This review exemplarily addresses present-day knowledge of selected AP2/EREBP with focus on a function in stress signal integration and retrograde signalling and defines AP2/EREBP-linked gene networks from transcriptional profiling-based graphical Gaussian models. The latter approach suggests highly interlinked functions of AP2/EREBPs in retrograde and stress signalling.

  2. Environmental, dietary, and hormonal factors in the regulation of seasonal breeding in free-living female Indian rose-ringed parakeets (Psittacula krameri).

    Science.gov (United States)

    Sailaja, R; Kotak, V C; Sharp, P J; Schmedemann, R; Haase, E

    1988-12-01

    The roles of environmental, dietary, and hormonal factors in the timing of seasonal breeding were assessed in free-living female Indian rose-ringed parakeets, Psittacula krameri, in northwest India (22 degrees 2'N, 73 degrees E). The ovaries and oviducts began to enlarge in January, were fully developed in February, and began to regress in March. During this time there was no significant change in the concentration of plasma luteinizing hormone (LH) or estradiol. The concentration of plasma LH decreased (P less than 0.01) at the end of the breeding season. Pair bond formation occurred between September and December and was associated with an increase in levels of plasma LH but no change in plasma estradiol. Concentrations of plasma testosterone (T) and 5 alpha-dihydrotestosterone (5 alpha-DHT) did not vary significantly during the year and were similar to those in males except for higher values of 5 alpha-DHT and lower values of T during the pre- and postbreeding periods, respectively. The similar levels of plasma androgens in both sexes may be related to the equal roles that both sexes play in the defence of their nest holes. An analysis of crop sac contents showed that the birds fed chiefly on pigeon peas (Cajanus cajan) during the breeding season and on cereal grains at other times of the year. It is suggested that pigeon peas provide the extra nutrients, including calcium, required for egg production. Since pigeon peas ripen between November and March, the production of the crop may play a role in the timing of seasonal breeding. A further factor appears to be competition for nest sites. By breeding in winter, the parakeet avoids competing with other species which nest in holes.

  3. Parentally-adjusted deficit of height as a prognostic factor of the effectiveness of growth hormone (GH) therapy in children with GH deficiency.

    Science.gov (United States)

    Hilczer, Maciej; Smyczyńska, Joanna; Lewiński, Andrzej

    2006-01-01

    Parental height is the most important identifiable factor influencing final height (FH) of children with growth hormone (GH) deficiency (GHD), treated with GH. Assessment of FH of patients with GHD--classified into familial short stature (FSS) and non-familial short stature (non-FSS) according to parentally adjusted deficit of height. The analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height was compared with patients' height before GH therapy, predicted adult height (PAH) and target height (TH). Both GH peak in stimulating tests and height standard deviation score (SDS) before the therapy were significantly lower in non-FSS than in FSS. Target height was significantly lower in FSS than in non-FSS. Parentally-adjusted deficit of height was significantly more profound in non-FSS than in FSS. The prognosis of adult height was very similar in both groups of patients, being significantly worse in non-FSS than in FSS while corrected by TH. The absolute FH was similar in FSS and non-FSS, being, however, significantly lower in non-FSS than in FSS while corrected by TH. Improvement of height was significantly better in non-FSS than in FSS. In both groups, FH SDS was significantly better than height SDS before the therapy (H0SDS). In FSS group, PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS group FH was significantly higher than PAH, but both FH and PAH were significantly lower than TH. 1) Growth hormone therapy was more effective in the patients with non-FSS than in those with FSS. 2) Parentally-adjusted deficit of height is an important prognostic factor of GH therapy effectiveness.

  4. OsWRKY74, a WRKY transcription factor, modulates tolerance to phosphate starvation in rice.

    Science.gov (United States)

    Dai, Xiaoyan; Wang, Yuanyuan; Zhang, Wen-Hao

    2016-02-01

    The WRKY transcription factor family has 109 members in the rice genome, and has been reported to be involved in the regulation of biotic and abiotic stress in plants. Here, we demonstrated that a rice OsWRKY74 belonging to group III of the WRKY transcription factor family was involved in tolerance to phosphate (Pi) starvation. OsWRKY74 was localized in the nucleus and mainly expressed in roots and leaves. Overexpression of OsWRKY74 significantly enhanced tolerance to Pi starvation, whereas transgenic lines with down-regulation of OsWRKY74 were sensitive to Pi starvation. Root and shoot biomass, and phosphorus (P) concentration in rice OsWRKY74-overexpressing plants were ~16% higher than those of wild-type (WT) plants in Pi-deficient hydroponic solution. In soil pot experiments, >24% increases in tiller number, grain weight and P concentration were observed in rice OsWRKY74-overexpressing plants compared to WT plants when grown in P-deficient medium. Furthermore, Pi starvation-induced changes in root system architecture were more profound in OsWRKY74-overexpressing plants than in WT plants. Expression patterns of a number of Pi-responsive genes were altered in the OsWRKY74-overexpressing and RNA interference lines. In addition, OsWRKY74 may also be involved in the response to deficiencies in iron (Fe) and nitrogen (N) as well as cold stress in rice. In Pi-deficient conditions, OsWRKY74-overexpressing plants exhibited greater accumulation of Fe and up-regulation of the cold-responsive genes than WT plants. These findings highlight the role of OsWRKY74 in modulation of Pi homeostasis and potential crosstalk between P starvation and Fe starvation, and cold stress in rice. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Factors influencing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies

    International Nuclear Information System (INIS)

    Georg, Petra; Georg, Dietmar; Hillbrand, Martin; Kirisits, Christian; Poetter, Richard

    2006-01-01

    Background and purpose: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. Patients and methods: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group 'DEF') and 10 endometrial cancer patients treated postoperatively (group 'POST'). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4 Gy) were compared in terms of DVH and various target parameters. Results: At doses between 40 and 50.4 Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4 Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. Conclusions: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50 Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing

  6. Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.

    Science.gov (United States)

    Pahwa, Roma; Kumar, Uma; Das, Nibhriti

    2016-03-01

    Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.

  7. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation.

    Science.gov (United States)

    Azmi, Peter; Seth, Arun

    2005-11-01

    Our laboratory has found that the 154aa RING finger protein 11 (RNF11), has modular domains and motifs including a RING-H2 finger domain, a PY motif, an ubiquitin interacting motif (UIM), a 14-3-3 binding sequence and an AKT phosphorylation site. RNF11 represents a unique protein with no other known immediate family members yet described. Comparative genetic analysis has shown that RNF11 is highly conserved throughout evolution. This may indicate a conserved and non-redundant role for the RNF11 protein. Molecular binding assays using RNF11 have shown that RNF11 has important roles in growth factor signalling, ubiquitination and transcriptional regulation. RNF11 has been shown to interact with HECT-type E3 ubiquitin ligases Nedd4, AIP4, Smurf1 and Smurf2, as well as with Cullin1, the core protein in the multi-subunit SCF E3 ubiquitin ligase complex. Work done in our laboratory has shown that RNF11 is capable of antagonizing Smurf2-mediated inhibition of TGFbeta signalling. Furthermore, RNF11 is capable of degrading AMSH, a positive regulator of both TGFbeta and EGFR signalling pathways. Recently, we have found that RNF11 can directly enhance TGFbeta signalling through a direct association with Smad4, the common signal transducer and transcription factor in the TGFbeta, BMP, and Activin pathways. Through its association with Smad4 and other transcription factors, RNF11 may have a role in direct transcriptional regulation. Our laboratory and others have found nearly 80 protein interactions for RNF11, placing RNF11 at the cross-roads of cell signalling and transcriptional regulation. RNF11 is highly expressed in breast tumours. Deregulation of RNF11 function may prove to be harmful to patient therapeutic outcomes. RNF11 may therefore provide a novel target for cancer therapeutics. The purpose of this review is to discuss the role of RNF11 in cell signalling and transcription factor modulation with special attention given to the ubiquitin-proteasomal pathway, TGFbeta

  8. Effects of hormones on platelet aggregation.

    Science.gov (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

    2014-04-01

    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  9. Thyroid stimulating hormone receptor (TSHR intron 1 variants are major risk factors for Graves' disease in three European Caucasian cohorts.

    Directory of Open Access Journals (Sweden)

    Rafał Płoski

    2010-11-01

    Full Text Available The thyroid stimulating hormone receptor (TSHR gene is an established susceptibility locus for Graves' disease (GD, with recent studies refining association to two single nucleotide polymorphisms (SNPs, rs179247 and rs12101255, within TSHR intron 1.We aimed to validate association of rs179247 and rs12101255 in Polish and UK Caucasian GD case-control subjects, determine the mode of inheritance and to see if association correlates with specific GD clinical manifestations. We investigated three case-control populations; 558 GD patients and 520 controls from Warsaw, Poland, 196 GD patients and 198 controls from Gliwice, Poland and 2504 GD patients from the UK National collection and 2784 controls from the 1958 British Birth cohort. Both rs179247 (P = 1.2×10(-2-6.2×10(-15, OR = 1.38-1.45 and rs12101255 (P = 1.0×10(-4-3.68×10(-21, OR = 1.47-1.87 exhibited strong association with GD in all three cohorts. Logistic regression suggested association of rs179247 is secondary to rs12101255 in all cohorts. Inheritance modeling suggested a co-dominant mode of inheritance in all cohorts. Genotype-phenotype correlations provided no clear evidence of association with any specific clinical characteristics.We have validated association of TSHR intron 1 SNPs with GD in three independent European cohorts and have demonstrated that the aetiological variant within the TSHR is likely to be in strong linkage disequilibrium with rs12101255. Fine mapping is now required to determine the exact location of the aetiological DNA variants within the TSHR.

  10. Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Postoperative Muscle and Substrate Metabolism

    Directory of Open Access Journals (Sweden)

    Folke Hammarqvist

    2010-01-01

    To conclude, growth factors influences urea metabolism, protein degradation and protein synthesis. There was no clearcut additional effect when combining GH and IGF-1 but the study was probably underpowered to outrule this and effects on nitrogen balance.

  11. Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

    Science.gov (United States)

    Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

    2017-01-01

    In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human

  12. Network analysis of S. aureus response to ramoplanin reveals modules for virulence factors and resistance mechanisms and characteristic novel genes.

    Science.gov (United States)

    Subramanian, Devika; Natarajan, Jeyakumar

    2015-12-10

    Staphylococcus aureus is a major human pathogen and ramoplanin is an antimicrobial attributed for effective treatment. The goal of this study was to examine the transcriptomic profiles of ramoplanin sensitive and resistant S. aureus to identify putative modules responsible for virulence and resistance-mechanisms and its characteristic novel genes. The dysregulated genes were used to reconstruct protein functional association networks for virulence-factors and resistance-mechanisms individually. Strong link between metabolic-pathways and development of virulence/resistance is suggested. We identified 15 putative modules of virulence factors. Six hypothetical genes were annotated with novel virulence activity among which SACOL0281 was discovered to be an essential virulence factor EsaD. The roles of MazEF toxin-antitoxin system, SACOL0202/SACOL0201 two-component system and that of amino-sugar and nucleotide-sugar metabolism in virulence are also suggested. In addition, 14 putative modules of resistance mechanisms including modules of ribosomal protein-coding genes and metabolic pathways such as biotin-synthesis, TCA-cycle, riboflavin-biosynthesis, peptidoglycan-biosynthesis etc. are also indicated. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  14. Asprosin, a fasting-induced glucogenic protein hormone

    Science.gov (United States)

    Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is t...

  15. Commensal bacteria modulate the tumor microenvironment.

    Science.gov (United States)

    Poutahidis, Theofilos; Erdman, Susan E

    2016-09-28

    It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Parathyroid hormone inhibition of Na{sup +}/H{sup +} exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves, E-mail: camilab@icb.usp.br; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na{sup +}/H{sup +} exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the −61 to −42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. - Highlights: • PTH regulation of Nhe3 promoter depends on EGR1 binding. • EGR1, PKA and JAK/STAT are involved in PTH inhibition of the Nhe3 promoter. • PTH alters expression of EGR1 and Sp3. • PTH inhibits the Nhe3 promoter by regulating PKA and JAK/STAT signaling.

  17. Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging.

    Science.gov (United States)

    Ratajczak, Mariusz Z; Bartke, Andrzej; Darzynkiewicz, Zbigniew

    2017-08-01

    The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.

  18. Levels of insulin, insulin-like growth factor-I and thyroid hormones in relation to the body condition score changes in periparturient dairy cows

    Directory of Open Access Journals (Sweden)

    Fratrić Natalija

    2013-01-01

    Full Text Available The objective of this study was to determine the levels of insulin, insulin like growth factor I (IGF-I and thyroid hormones in relation to the body condition score (BCS of periparturient dairy cows. The study was carried out on twenty Holstein-Friesian dairy cows with average milk production of 7000 L/305 days in the previous lactation, parity ranging from 2-4. All cows were BCS scored during the early dry period, 7±3 days before and after parturition. Based on the BCS at the early dry period, cows were divided in two groups: cows with high BCS (3.75- 4.25, HBCS, n=10, and cows with moderate BCS (2.75-3.75, MBCS, n=10. Blood samples were taken at the time of BCS evaluation. Concentrations of insulin, IGF-I, triiodothyroinine (T3 and thyroxine (T4 were determined by radioimmunoassay (RIA, INEP-Zemun, Serbia. Statistical differences between mean values were determined using Student t-test (p0.05. IGF-I level in HBCS cows at days 7±3 before calving was significantly higher (16.28±3.07:11.76±2.28, p<0.01, with a reverse relationship after calving (3.77±1.64:8.46±2.37, p<0.01. Insulin level was significantly lower at 7±3 days before calving in HBCS cows (16.26±4.60:20.18±4.96mIU/L, p<0.05. Thyroid hormones levels were significantly lower in HBCS group et all examined periods. [Projekat Ministarstva nauke Republike Srbije, br. III 46002 i br. 31003

  19. Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

    Science.gov (United States)

    André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

    2014-06-01

    International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

  20. Interleukin 1β, tumor necrosis factor-α and interleukin 6 decreas nuclear thyroid hormone receptor capacity in a liver cell line

    International Nuclear Information System (INIS)

    Wolf, M.; Hansen, N.; Greten, H.

    1994-01-01

    Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-α (TNTF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies the authors investigated in vitro whether TNF-α, IL-1β and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [ 125 I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1β decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 ± 3.9% after incubation with 0.1, 1.0 and 100 μg/l IL-1β, respectively. Interleukin 6 and TNF-α significantly reduced receptor capacity only at concentrations of 10μg/l or higher and the magnitude of the reduction was lower than with IL-1β. The TR capacity was reduced to 81.2 ± 2.3% and 83.2 ± 6.6% after stimulation with 10μg/l IL-6 or TNF-α, respectively. TR affinity was not altered significantly after stimulation with any of the cytokines. 44 refs., 4 figs

  1. Serum Levels Of Free And Total Insulin-Like Growth Factor (IGF)-1 And IGF Binding Protein-3 In Normal And Growth Hormone Deficient Children

    International Nuclear Information System (INIS)

    Shousha, M.A.; Soliman, S.E.T.; Hafez, M.H.

    2006-01-01

    Serum levels of total insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening growth hormone deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 pre-pubertal GH deficient (GHD) children to study the correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97-1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the pre-pubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD were decreased significantly with increasing the degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

  2. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    Science.gov (United States)

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  3. Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

    Science.gov (United States)

    Yuen, Kevin C J; Bennett, Robert M; Hryciw, Cheryl A; Cook, Marie B; Rhoads, Sharon A; Cook, David M

    2007-02-01

    Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

  4. Impact Factors Analysis of the Hot Side Temperature of Thermoelectric Module

    Science.gov (United States)

    Zhang, Xingyu; Tan, Gangfeng; Yang, Bo

    2018-03-01

    The thermoelectric generator (TEG) plays a crucial role in converting the waste energy of exhaust into electricity, which ensures energy saving and increased fuel utilization efficiency. In the urban driving cycle, frequent vehicle operation, like deceleration or acceleration, results in continuous variation of the exhaust temperature. In order to make the operating performance stable, and to weaken the adverse effects of the frequent variation of the exhaust temperature on the lifetime and work efficiency of the electronic components of TEG systems, the output voltage of the thermoelectric (TE) module should stay more stable. This article provides an improved method for the temperature stability of the TE material hot side based on sandwiching material. From the view of the TEG system's average output power and the hot side temperature stability of the TE material, the analyzing factors, including the fluctuation frequency of the exhaust temperature and the physical properties and thickness of the sandwiching material are evaluated, respectively, in the sine and new European driving cycle (NEDC) fluctuation condition of the exhaust temperature. The results show few effects of sandwiching material thickness with excellent thermal conductivity on the average output power. During the 150-170 s of the NEDC test condition, the minimum hot side temperatures with a BeO ceramic thickness of 2 mm and 6 mm are, respectively, 537.19 K and 685.70 K, which shows the obvious effect on the hot side temperature stability of the BeO ceramic thickness in the process of acceleration and deceleration of vehicle driving.

  5. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

    Science.gov (United States)

    Terao, Junji

    2017-09-01

    Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. NFκBP65 transcription factor modulates resistance to doxorubicin through ABC transporters in breast cancer.

    Science.gov (United States)

    Velaei, Kobra; Samadi, Nasser; Soltani, Sina; Barazvan, Balal; Soleimani Rad, Jafar

    2017-07-01

    Shedding light on chemoresistance biology of breast cancer could contribute to enhance the clinical outcome. Intrinsic or acquired resistance to chemotherapy is a major problem in breast cancer treatment. The NFκB pathway by siRNAP65 and JSH-23 as a translocational inhibitor of NFκBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7 cells was blocked. Then, the ABC transporter expression and function were assessed by real-time qRT-PCR and flow cytometry, respectively. Induction of apoptosis was evaluated after inhibition of the NFΚB pathway as well. Our study underlined the upregulation of NFκBP65 and anti-apoptotic Bcl-2 and downregulation of pro-apoptotic Bax in the MCF-7/Dox cells compared with control MCF-7 cells. Here, we showed that interplay between nuclear factor kappa B P65 (NFkBP65) as a transcriptional regulator and ABC transporters in the MCF-7/Dox cancer cells. We found that inhibition of the elevated expression of NFκBP65 in the resistant breast cancer, whether translocational inhibition or silencing by siRNA, decreased the expression and function of MDR1 and MRP1 efflux pumps. Furthermore, the blockade of NFκBP65 promoted apoptosis via modulating Bcl-2 and BAX expression. After inhibition of the NFκBP65 signaling pathway, elevated baseline expression of survival Bcl-2 gene in the resistant breast cells significantly decreased. Suppression of the NFκB pathway has a profound dual impact on promoting the intrinsic apoptotic pathway and reducing ABC transporter function and expression, which are some of the chemoresistance features. It was speculated that the NFκB pathway directly acts on doxorubicin-induced MDR1 and MRP1 expression in MCF-7/Dox cells.

  7. Downregulation of SWI/SNF chromatin remodeling factor subunits modulates cisplatin cytotoxicity

    International Nuclear Information System (INIS)

    Kothandapani, Anbarasi; Gopalakrishnan, Kathirvel; Kahali, Bhaskar; Reisman, David; Patrick, Steve M.

    2012-01-01

    Chromatin remodeling complex SWI/SNF plays important roles in many cellular processes including transcription, proliferation, differentiation and DNA repair. In this report, we investigated the role of SWI/SNF catalytic subunits Brg1 and Brm in the cellular response to cisplatin in lung cancer and head/neck cancer cells. Stable knockdown of Brg1 and Brm enhanced cellular sensitivity to cisplatin. Repair kinetics of cisplatin DNA adducts revealed that downregulation of Brg1 and Brm impeded the repair of both intrastrand adducts and interstrand crosslinks (ICLs). Cisplatin ICL-induced DNA double strand break repair was also decreased in Brg1 and Brm depleted cells. Altered checkpoint activation with enhanced apoptosis as well as impaired chromatin relaxation was observed in Brg1 and Brm deficient cells. Downregulation of Brg1 and Brm did not affect the recruitment of DNA damage recognition factor XPC to cisplatin DNA lesions, but affected ERCC1 recruitment, which is involved in the later stages of DNA repair. Based on these results, we propose that SWI/SNF chromatin remodeling complex modulates cisplatin cytotoxicity by facilitating efficient repair of the cisplatin DNA lesions. -- Highlights: ► Stable knockdown of Brg1 and Brm enhances cellular sensitivity to cisplatin. ► Downregulation of Brg1 and Brm impedes the repair of cisplatin intrastrand adducts and interstrand crosslinks. ► Brg1 and Brm deficiency results in impaired chromatin relaxation, altered checkpoint activation as well as enhanced apoptosis. ► Downregulation of Brg1 and Brm affects recruitment of ERCC1, but not XPC to cisplatin DNA lesions.

  8. Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Tsuneyuki [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Mitsuhiro, E-mail: m_nkmr@kuhp.kyoto-u.ac.jp [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Hirose, Yoshinori; Kitsuda, Kenji; Notogawa, Takuya; Miki, Katsuhito [Division of Radiology, Osaka Red Cross Hospital, Osaka (Japan); Nakamura, Kiyonao; Ishigaki, Takashi [Department of Radiation Oncology, Osaka Red Cross Hospital, Osaka (Japan)

    2014-01-01

    We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D{sub 95%}), and percentage of prostate volume covered by the 100% isodose line (V{sub 100%}) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COM{sub AP}) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COM{sub AP} and prostate D{sub 95%} and V{sub 100%} were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D{sub 95%} and V{sub 100%}. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

  9. Investigation of a thiazolidinone derivative as an allosteric modulator of follicle stimulating hormone receptor: evidence for its ability to support follicular development and ovulation.

    Science.gov (United States)

    Sriraman, Venkataraman; Denis, Deborah; de Matos, Daniel; Yu, Henry; Palmer, Stephen; Nataraja, Selva

    2014-05-15

    FSH signalling through its cognate receptor is critical for follicular development and ovulation. An earlier study had documented thiazolidinone derivatives to activate FSH receptor expressed in CHO cells and rat granulosa cells; however development of this compound for clinical use was halted for unobvious reasons. The objective of the current study is to extend the previous investigations in detail on the ability of thiazolidinone derivative (henceforth referred to as Compound 5) to activate FSH signalling and learn the barriers that preclude development of this derivative for clinical purposes. Our results demonstrate that the Compound 5 in a dose-dependent manner stimulated cAMP production, activated AKT and ERK signalling pathways and induced estradiol production in cultured rat granulosa cells. Compound 5 also caused dose-dependent increase in estradiol production from human granulosa cells. In increasingly more complex in vitro systems, Compound 5 was able to induce the expansion of mouse cumulus-oocyte-complex and support in vitro development of mouse preantral follicle to preovulatory stage and release of oocyte from the follicle. In vivo, the compound stimulated preovulatory follicular development and ovulation in immature rats. Pharmacokinetic and safety investigations reveal poor oral availability and genotoxicity. Together, our results document Compound 5 to act as a FSHR allosteric modulator but have poor pharmacological properties for development of an oral FSH receptor modulator. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

    Directory of Open Access Journals (Sweden)

    Seok Joo Park

    2014-09-01

    Full Text Available BackgroundIt has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH/insulin-like growth factor-1 (IGF-1.MethodsIn this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice.ResultsThe GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt/phospho-glycogen synthase kinase3β (p-GSK3β, phospho-extracellular signal-related kinase (p-ERK, and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK, Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist.ConclusionThe results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

  11. Identification and characterization of a novel nanobody against human placental growth factor to modulate angiogenesis.

    Science.gov (United States)

    Arezumand, Roghaye; Mahdian, Reza; Zeinali, Sirous; Hassanzadeh-Ghassabeh, Gholamreza; Mansouri, Kamran; Khanahmad, Hossein; Namvar-Asl, Nabiollah; Rahimi, Hamzeh; Behdani, Mahdi; Cohan, Reza Ahangari; Eavazalipour, Mehdi; Ramazani, Ali; Muyldermans, Serge

    2016-10-01

    Placental growth factor (PlGF), a member of vascular endothelial growth factors (VEGF) family, is considered as an important antigen associated with pathological conditions such as cancer cell growth, and metastasis. PlGF-targeting via nanobody (Nb) therefore could be beneficial to modulate these pathologies. In this work, phage-display and computational approach was employed to develop a high affinity PlGF-specific Nb. An Nb library was constructed against human recombinant PlGF (rPlGF). After panning on immobilized rPlGF the periplasmic-extract (PE) of individual colonies were screened by ELISA (PE-ELISA). The 3D structures of selected Nbs were then homology modeled and energy minimized using the AMBER force field. Binding score calculations were also assessed to reveal possible Nb-PlGF interactions. Via ELISA-based affinity/specificity determinations, the best-qualified Nb was further evaluated by proliferation, migration, 3D capillary formation, invasion assays and on Chick chorioallantoic membrane (CAM) model. An immune library of 1.5×10 7 individual Nb clones was constructed. By PE-ELISA 12 clones with strong signals were selected. Three out of 12 sequenced Nbs (Nb-C13, Nb-C18 and Nb-C62) showed high binding scores ranging between -378.7 and -461kcal/mol. Compared to a control Nb, Nb-C18 significantly inhibited proliferation, migration and the 3D-capillary formation of HUVEC cells (p<0.05) with an EC 50 of 35nM, 42nM and 24nM and invasion of MDA-MB231was significantly suppressed (p<0.05) with an EC 50 of57nM. The result of the CAM assay shows that Nb-C18 could inhibit the vascular formation in the chicken chorioallantoic membrane. This Nb can be used as anti-angiogenesis agent in future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Pigment-dispersing factor modulates pheromone production in clock cells that influence mating in Drosophila

    NARCIS (Netherlands)

    Krupp, Joshua J.; Billeter, Jean-Christophe; Wong, Amy; Choi, Charles; Nitabach, Michael N.; Levine, Joel D.

    2013-01-01

    Social cues contribute to the circadian entrainment of physiological and behavioral rhythms. These cues supplement the influence of daily and seasonal cycles in light and temperature. In Drosophila, the social environment modulates circadian mechanisms that regulate sex pheromone production and

  13. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  14. Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury.

    Science.gov (United States)

    Boo, Stellar; Dagnino, Lina

    2013-06-01

    Abnormal wound repair results from disorders in granulation tissue remodeling, and can lead to hypertrophic scarring and fibrosis. Excessive scarring can compromise tissue function and decrease tissue resistance to additional injuries. The development of potential therapies to minimize scarring is, thus, necessary to address an important clinical problem. It has been clearly established that multiple cytokines and growth factors participate in the regulation of cutaneous wound healing. More recently, it has become apparent that these factors do not necessarily activate isolated signaling pathways. Rather, in some cases, there is cross-modulation of several cellular pathways involved in this process. Two of the key pathways that modulate each other during wound healing are activated by transforming growth factor-β and by extracellular matrix proteins acting through integrins. The pathogenesis of excessive scarring upon wound healing is not fully understood, as a result of the complexity of this process. However, the fact that many pathways combine to produce fibrosis provides multiple potential therapeutic targets. Some of them have been identified, such as focal adhesion kinase and integrin-linked kinase. Currently, a major challenge is to develop pharmacological inhibitors of these proteins with therapeutic value to promote efficient wound repair. The ability to better understand how different pathways crosstalk during wound repair and to identify and pharmacologically modulate key factors that contribute to the regulation of multiple wound-healing pathways could potentially provide effective therapeutic targets to decrease or prevent excessive scar formation and/or development of fibrosis.

  15. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    International Nuclear Information System (INIS)

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-01-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

  16. Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.

    Science.gov (United States)

    Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L

    1999-05-01

    Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P deficit by increasing those parameters of prostate development (P growth as an extension of a normal process.

  17. Relative Risks of Contributing Factors to Morbidity and Mortality in Adults With Craniopharyngioma on Growth Hormone Replacement.

    Science.gov (United States)

    Yuen, Kevin C J; Mattsson, Anders F; Burman, Pia; Erfurth, Eva-Marie; Camacho-Hubner, Cecilia; Fox, Janet L; Verhelst, Johan; Geffner, Mitchell E; Abs, Roger

    2018-02-01

    In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or adult-onset (AO-CP) is associated with increased morbidity and mortality, but data on the relative risks (RRs) of contributing factors are lacking. To assess the RRs of factors contributing to morbidity and mortality in adults with CO-CP and AO-CP. Data on 1669 patients with CP from KIMS (Pfizer International Metabolic Database) were analyzed using univariate and multiple Poisson and Cox regression methods. When CO-CP and AO-CP groups were combined, history of stroke and hyperlipidemia increased cardiovascular risk, higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and increased waist circumference increased the risk of developing diabetes mellitus (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold higher risk of tumor recurrence, whereas being female and previous radiotherapy exposure conferred lower risks. Radiotherapy and older age with every 10 years from disease onset conferred a 2.3- to 3.5-fold risk for developing new intracranial tumors, whereas older age, greater and/or increasing BMI, history of stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score measured at last sampling before death were related to increased all-cause mortality. Compared with the general population, adults with CP had 9.3-, 8.1-, and 2.2-fold risks of developing DM, new intracranial tumors, and early death, respectively. Conventional factors that increase the risks of cardio- and cerebrovascular diseases and DM and risks for developing new intracranial tumors contributed to excess morbidity and mortality. In addition, lower serum IGF-I level measured from the last sample before death was inversely associated with mortality risk in patients with CP. Copyright © 2017 Endocrine Society

  18. Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae

    International Nuclear Information System (INIS)

    Kream, B.E.; Petersen, D.N.; Raisz, L.G.

    1990-01-01

    We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of [ 3 H]proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways

  19. Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles

    Science.gov (United States)

    Liem, Giok S.; Mo, Frankie K. F.; Pang, Elizabeth; Suen, Joyce J. S.; Tang, Nelson L. S.; Lee, Kun M.; Yip, Claudia H. W.; Tam, Wing H.; Ng, Rita; Koh, Jane; Yip, Christopher C. H.; Kong, Grace W. S.; Yeo, Winnie

    2015-01-01

    Purpose In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. Methods Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3–10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients’ background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. Results 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. Conclusion After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake. PMID:26485568

  20. Expression of serum insulin-like growth factors, insulin-like growth factor-binding proteins, and the growth hormone-binding protein in heterozygote relatives of Ecuadorian growth hormone receptor deficient patients.

    Science.gov (United States)

    Fielder, P J; Guevara-Aguirre, J; Rosenbloom, A L; Carlsson, L; Hintz, R L; Rosenfeld, R G

    1992-04-01

    Recently, an isolated population of apparent GH-receptor deficient (GHRD) patients has been identified in the Loja province of southern Ecuador. These individuals presented many of the physical and biochemical phenotypes characteristic of Laron-Syndrome and are believed to have a defect in the GH-receptor gene. In this study, we have compared the biochemical phenotypes between the affected individuals and their parents, considered to be obligate heterozygotes for the disorder. Serum GH, insulin-like growth factor I and II (IGF-I and IGF-II) levels were measured by RIA Insulin-like growth factor binding proteins. (IGFBPs) were measured by Western ligand blotting (WLB) of serum samples, following separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and relative quantitation of serum IGFBPs was performed with a scanning laser densitometer. Serum GH-binding protein (GHBP) levels were measured with a ligand-mediated immunofunctional assay using a monoclonal antibody raised against the GHBP. These values were then compared to values obtained from normal, sex-matched adult Ecuadorian controls, to determine if the above parameters were abnormal in the heterozygotes. The serum IGF-I levels of the GHRD patients were less than 13% of control values for adults and 2% for children. However, the IGF-I levels of both the mothers and fathers were not significantly different from that of the control population. The serum IGF-II levels of the GHRD patients were approximately 20% of control values for adults and 12% for the children. The IGF-II levels of the mothers were reduced, but were not significantly different from that of the control population. However, IGF-II levels of the fathers were significantly lower than those of controls (64% of control male levels). WLB analysis of serum IGFBP levels of the affected subjects demonstrated increased IGFBP-2 and decreased IGFBP-3, suggesting an inverse relationship between these IGFBPs. The GHRD patients who had the

  1. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio).

    Science.gov (United States)

    Zhao, Yali; Lin, Meng-Chin A; Mock, Allan; Yang, Ming; Wayne, Nancy L

    2014-01-01

    Kisspeptin1 (product of the Kiss1 gene) is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH) neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r) are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while Kiss2 plays an

  2. Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Yali Zhao

    Full Text Available Kisspeptin1 (product of the Kiss1 gene is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while

  3. Association Between Thyroid Hormones, Thyroid Antibodies, and Cardiometabolic Factors in Non-Obese Individuals With Normal Thyroid Function

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    Jia Liu

    2018-04-01

    Full Text Available BackgroundHypothyroidism is an important risk factor for cardiovascular diseases, and autoimmune thyroiditis (AIT is the leading cause of hypothyroidism. Recent studies showed that even AIT patients with euthyroidism still had an increased number of early atherosclerotic lesions. However, the precise mechanism is not yet known. This study aimed to investigate the association of thyroid function, thyroid autoimmunity, and cardiometabolic risk factors in non-obese AIT patients with euthyroidism.MethodsA total of 5,608 non-obese individuals including 1,402 AIT patient and 4,206 sex-, age-, and body mass index (BMI-matched healthy controls were recruited.ResultsThe AIT patients had significantly lower free T3 and free T4 levels, and higher TSH, antithyroid peroxidase antibodies (TPOAb and TgAb levels. The elevated levels of high sensitivity C reactive protein (hsCRP and homeostasis model assessment of insulin resistance (HOMA-IR were observed in the AIT patients than the controls [hsCRP: 0.65 (0.27–1.33 vs. 0.20 (0.03–0.74 mg/L; HOMA-IR: 2.78 ± 1.60 vs. 2.33 ± 1.49; all P < 0.05]. Thyroid function was not associated with metabolic parameters and inflammatory makers, while the TPOAb titer was positively associated with the HOMA-IR and hsCRP levels after adjustment for confounding factors (all P < 0.05. Multivariate regression analysis demonstrated that the TPOAb level was an independent influencing factor