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Sample records for hormone releasing factor

  1. 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...

  2. Active immunization of pigs against growth hormone-releasing factor: effect on concentrations of growth hormone and insulin-like growth factor 1.

    Science.gov (United States)

    Armstrong, J D; Esbenshade, K L; Johnson, J L; Coffey, M T; Heimer, E; Campbell, R M; Mowles, T; Felix, A

    1990-02-01

    Cyclic gilts (96 +/- 1 kg) were used to determine the effect of active immunization against growth hormone-releasing factor GRF(1-29)-NH2 on concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Gilts were immunized against GRF conjugated to human serum albumin (GRF-HSA, n = 5) or HSA alone at 180 d of age (wk 0). Booster doses were administered at wk 9 and 13. Seven days after the second booster (wk 14), blood samples were collected at 15-min intervals for 6 h before feeding and 30, 60, 120, 180 and 240 min after feeding. Eight days after the second booster, all gilts were administered a GRF analog, [desNH2Tyr1,Ala15]-GRF(1-29)-NH2, followed by an opioid agonist, FK33-824. Blood samples were collected at 15-min intervals from -30 to 240 min after injection. Immunization against GRF-HSA resulted in antibody titers, expressed as dilution required to bind 50% of [125I]GRF, ranging from 1:11,000 to 1:60,000 (wk 11 and 14); binding was not detectable or was less than 50% at 1:100 in HSA gilts (P less than .05). Episodic release of GH was abolished by immunization against GRF-HSA (P less than .05). Mean GH was decreased (P less than .07), but basal GH concentrations were not altered (P greater than .15) by immunization against GRF-HSA. Serum concentrations of IGF-1 were similar at wk 0, but concentrations were lower in GRF-HSA than in HSA gilts (P less than .05) at wk 14.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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...

  4. Neither bST nor Growth Hormone Releasing Factor Alter Expression of Thyroid Hormone Receptors in Liver and Mammary Tissues

    Science.gov (United States)

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine, to specific nuclear receptors. It has been hypothesized that organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, target the action of thyroid hormones to the mammary...

  5. 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.

  6. Effects of active immunization against growth-hormone releasing factor on puberty and reproductive development in gilts.

    Science.gov (United States)

    Swanchara, K W; Armstrong, J D; Britt, J H

    1999-07-01

    Hormones within the somatotropin cascade influence several physiological traits, including growth and reproduction. Active immunization against growth hormone-releasing factor (GRFi) initiated at 3 or 6 mo of age decreased weight gain, increased deposition of fat, and delayed puberty in heifers. Two experiments were conducted to investigate the effects of GRFi on puberty and subsequent ovulation rate in gilts. Crossbred gilts were actively immunized against GRF-(1-29)-(Gly)2-Cys-NH2 conjugated to human serum albumin (GRFi) or against human serum albumin alone (HSAi). In Exp. 1, gilts were immunized against GRF (n = 12) or HSA (n = 12) at 92 +/- 1 d of age. At 191 d of age, antibody titers against GRF were greater (P gilts. The GRFi decreased (P gilts were immunized against GRF (n = 35) or HSA (n = 35) at 35 +/- 1 d of age. The GRFi at 35 d of age did not alter the number of surface follicles or uterine weight between 93 and 102 d of age, but GRFi decreased (P Immunization against GRF reduced (P gilts, but ovulation rate was lower (P gilts. Thus, GRFi at 92 or 35 d of age decreased serum ST, IGF-I, and BW in prepubertal gilts without altering age of puberty. However, GRFi at 35 d of age, but not 92 d of age, decreased ovulation rate. These results indicate that alterations in the somatotropic axis at 1 mo of age can influence reproductive development in pubertal gilts.

  7. Alpha-melanocyte-stimulating hormone attenuates behavioral effects of corticotropin-releasing factor in isolated guinea pig pups.

    Science.gov (United States)

    Schiml-Webb, Patricia A; Miller, Emily; Deak, Terrence; Hennessy, Michael B

    2009-07-01

    During a 3-hr period of social isolation in a novel environment, guinea pig pups exhibit an initial active phase of behavioral responsiveness, characterized primarily by vocalizing, which is then followed by a stage of passive responsiveness in which pups display a distinctive crouch, eye-closing, and extensive piloerection. Prior treatment of pups with alpha-melanocyte-stimulating hormone (alpha-MSH) reduces each of the passive behaviors. The onset of passive responding during separation can be accelerated with peripheral injection of corticotropin-releasing factor (CRF). To examine whether CRF produces its effects through a mechanism similar to that of prolonged separation, we examined the effect of administering alpha-MSH to pups injected with CRF. As expected, CRF markedly enhanced passive responding during a 60-min period of separation. alpha-MSH delivered by either intracerebroventricular infusion or intraperitoneal injection significantly reduced each of the passive behavioral responses without significantly affecting active behavior. These findings, together with previous results indicating that it is the anti-inflammatory property of alpha-MSH that is responsible for its behavioral effects during prolonged separation, suggest that peripheral CRF speeds the induction of passive responding through a mechanism involving enhanced proinflammatory activity.

  8. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    Science.gov (United States)

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand. © 2015 British Society for Neuroendocrinology.

  9. Growth hormone releasing hormone or growth hormone treatment in growth hormone insufficiency?

    OpenAIRE

    Smith, P J; Brook, C G

    1988-01-01

    Sixteen prepubertal children who were insufficient for growth hormone were treated with growth hormone releasing hormone (GHRH) 1-40 and GHRH 1-29 for a mean time of nine months (range 6-12 months) with each peptide. Eleven children received GHRH 1-40 in four subcutaneous nocturnal pulses (dose 4-8 micrograms/kg/day) and eight (three of whom were also treated with GHRH 1-40) received GHRH 1-29 twice daily (dose 8-16 micrograms/kg/day). Altogether 73% of the children receiving GHRH 1-40 and 63...

  10. Corticotropin-releasing hormone and dopamine release in healthy individuals.

    Science.gov (United States)

    Payer, Doris; Williams, Belinda; Mansouri, Esmaeil; Stevanovski, Suzanna; Nakajima, Shinichiro; Le Foll, Bernard; Kish, Stephen; Houle, Sylvain; Mizrahi, Romina; George, Susan R; George, Tony P; Boileau, Isabelle

    2017-02-01

    Corticotropin-releasing hormone (CRH) is a key component of the neuroendocrine response to stress. In animal models, CRH has been shown to modulate dopamine release, and this interaction is believed to contribute to stress-induced relapse in neuropsychiatric disorders. Here we investigated whether CRH administration induces dopamine release in humans, using positron emission tomography (PET). Eight healthy volunteers (5 female, 22-48 years old) completed two PET scans with the dopamine D2/3 receptor radioligand [11C]-(+)-PHNO: once after saline injection, and once after injection of corticorelin (synthetic human CRH). We also assessed subjective reports and measured plasma levels of endocrine hormones (adrenocorticotropic hormone and cortisol). Relative to saline, corticorelin administration decreased binding of the D2/3 PET probe [11C]-(+)-PHNO, suggesting dopamine release. Endocrine stress markers were also elevated, in line with activation of the hypothalamic-pituitary-adrenal axis, but we detected no changes in subjective ratings. Preliminary results from this proof-of-concept study suggests that CRH challenge in combination with [11C]-(+)-PHNO PET may serve as an assay of dopamine release, presenting a potential platform for evaluating CRH/dopamine interactions in neuropsychiatric disorders and CRH antagonists as potential treatment avenues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Stimulatory effects of insulin-like growth factor 1 on expression of gonadotropin subunit genes and release of follicle-stimulating hormone and luteinizing hormone in masu salmon pituitary cells early in gametogenesis.

    Science.gov (United States)

    Furukuma, Shunji; Onuma, Takeshi; Swanson, Penny; Luo, Qiong; Koide, Nobuhisa; Okada, Houji; Urano, Akihisa; Ando, Hironori

    2008-01-01

    Insulin-like growth factor-I (IGF-I) has been shown to be involved in pubertal activation of gonadotropin (GTH) secretion. The aim of this study was to determine if IGF-I directly stimulates synthesis and release of GTH at an early stage of gametogenesis. The effects of IGF-I on expression of genes encoding glycoprotein alpha (GPalpha), follicle-stimulating hormone (FSH) beta, and luteinizing hormone (LH) beta subunits and release of FSH and LH were examined using primary pituitary cells of masu salmon at three reproductive stages: early gametogenesis, maturing stage, and spawning. IGF-I alone or IGF-I + salmon GnRH (sGnRH) were added to the primary pituitary cell cultures. Amounts of GPalpha, FSHbeta, and LHbeta mRNAs were determined by real-time PCR. Plasma and medium levels of FSH and LH were determined by RIA. In males, IGF-I increased the amounts of all three subunit mRNAs early in gametogenesis in a dose-dependent manner, but not in the later stages. In females, IGF-I stimulated release of FSH and LH early in gametogenesis, whereas no stimulatory effects on the subunit mRNA levels were observed at any stage. IGF-I + sGnRH stimulated release of FSH and LH at all stages in both sexes, but had different effects on the subunit mRNA levels depending on subunit and stage. The present results suggest that IGF-I itself directly stimulates synthesis and release of GTH early in gametogenesis in masu salmon, possibly acting as a metabolic signal that triggers the onset of puberty.

  12. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

    Science.gov (United States)

    Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

    2012-01-01

    OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (pgrowth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

  13. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.

    Directory of Open Access Journals (Sweden)

    Alexandra Mangili

    Full Text Available Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT in human immunodeficiency virus (HIV-infected patients with lipodystrophy.1 To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF or the National Cholesterol Education Program (MetS-NCEP and the Framingham Risk Score (FRS, as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2 To explore the characteristics of patients who reached a threshold of VAT 1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively. No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI and baseline VAT (95% confidence interval [CI] 2.03; 7.44.Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.

  14. Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

    Science.gov (United States)

    Harvey, S; Gineste, C; Gaylinn, B D

    2014-08-01

    Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    Science.gov (United States)

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

  16. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

    2013-01-01

    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  17. Expression patterns of corticotropin-releasing factor, arginine vasopressin, histidine decarboxylase, melanin-concentrating hormone, and orexin genes in the human hypothalamus.

    Science.gov (United States)

    Krolewski, David M; Medina, Adriana; Kerman, Ilan A; Bernard, Rene; Burke, Sharon; Thompson, Robert C; Bunney, William E; Schatzberg, Alan F; Myers, Richard M; Akil, Huda; Jones, Edward G; Watson, Stanley J

    2010-11-15

    The hypothalamus regulates numerous autonomic responses and behaviors. The neuroactive substances corticotropin-releasing factor (CRF), arginine-vasopressin (AVP), histidine decarboxylase (HDC), melanin-concentrating hormone (MCH), and orexin/hypocretins (ORX) produced in the hypothalamus mediate a subset of these processes. Although the expression patterns of these genes have been well studied in rodents, less is known about them in humans. We combined classical histological techniques with in situ hybridization histochemistry to produce both 2D and 3D images and to visually align and quantify expression of the genes for these substances in nuclei of the human hypothalamus. The hypothalamus was arbitrarily divided into rostral, intermediate, and caudal regions. The rostral region, containing the paraventricular nucleus (PVN), was defined by discrete localization of CRF- and AVP-expressing neurons, whereas distinct relationships between HDC, MCH, and ORX mRNA-expressing neurons delineated specific levels within the intermediate and caudal regions. Quantitative mRNA signal intensity measurements revealed no significant differences in overall CRF or AVP expression at any rostrocaudal level of the PVN. HDC mRNA expression was highest at the level of the premammillary area, which included the dorsomedial and tuberomammillary nuclei as well as the dorsolateral hypothalamic area. In addition, the overall intensity of hybridization signal exhibited by both MCH and ORX mRNA-expressing neurons peaked in distinct intermediate and caudal hypothalamic regions. These results suggest that human hypothalamic neurons involved in the regulation of the HPA axis display distinct neurochemical patterns that may encompass multiple local nuclei. Copyright © 2010 Wiley-Liss, Inc.

  18. Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1990-01-01

    It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH...

  19. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  20. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology

    NARCIS (Netherlands)

    Al-Inany, Hesham G.; Youssef, Mohamed A.; Ayeleke, Reuben Olugbenga; Brown, Julie; Lam, Wai Sun; Broekmans, Frank J.

    2016-01-01

    Background: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists

  1. Effects of hypothalamic dopamine on growth hormone-releasing hormone-induced growth hormone secretion and thyrotropin-releasing hormone-induced prolactin secretion in goats.

    Science.gov (United States)

    Jin, Jin; Hashizume, Tsutomu

    2015-06-01

    The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH-releasing response to an intravenous (i.v.) injection of GH-releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L-dopa (1 mg/kg BW) in male and female goats under a 16-h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L-dopa treatments completely suppressed GH-releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)-releasing response to an i.v. injection of thyrotropin-releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L-dopa significantly reduced TRH-induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats. © 2014 Japanese Society of Animal Science.

  2. Body fat affects mouse reproduction, ovarian hormone release, and response to follicular stimulating hormone.

    Science.gov (United States)

    Sirotkin, Alexander V; Fabian, Dušan; Babeľová Kubandová, Janka; Vlčková, Radoslava; Alwasel, Saleh; Harrath, Abdel Halim

    2017-12-07

    We investigated the effects of body fat content on mouse fecundity, ovarian hormone release, and their response to follicle stimulation hormone (FSH). 4 types of females were produced: lean (group 1), normal (group 2), slightly fat (group 3), and significantly fat (group 4). The body weights, fat content, fertility rate, embryo number produced, retarded and degenerated embryo percentage, the release of progesterone (P4), testosterone (T), and insulin-like growth factor I (IGF-I) by isolated ovaries cultured with and without FSH (1.0IU/mL medium) were evaluated. A gradual increase in body weight and fat contents from groups 1 to 4 was observed. Group 2 had higher fertility rate than those from the other groups. Groups 2 and 3 had fewer retarded and degenerated embryos that those from groups 1 and 4. Embryo production rate was not different among the groups. P4 and T secretion was higher from group 4 than in those from groups 1-3; secretion of IGF-I of group 3 was less than that of groups 1, 2, and 4. FSH promoted ovarian T output in all groups and stimulated ovarian P4 release in groups 1, 3, and 4, but not in group 2. FSH did not affect IGF-I release in any group. Therefore, both malnutrition and overfeeding can affect body weight and fat content in female mice, reducing embryo quality or developmental capacity, but not fertility and embryo production. Excess weight or fat can have stimulatory effects on ovarian P4 and T, but inhibitory effects on ovarian IGF-I release. Both leanness and excess weight or fat can induce the stimulatory action of FSH on ovarian P4. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. Protection of germinal epithelium with luteinizing hormone-releasing hormone analogue

    Energy Technology Data Exchange (ETDEWEB)

    Nseyo, U.O.; Huben, R.P.; Klioze, S.S.; Pontes, J.E.

    1985-07-01

    A dog model for chemotherapy and radiation-induced testicular damage was created to study the protective potential of superactive analogue of luteinizing hormone-releasing hormone, buserelin. Buserelin appeared to offer protection of the canine germinal epithelium against cyclophosphamide, cisplatinum and radiation. Clinical trials with buserelin in patients of reproductive age undergoing treatment for cancer should be encouraged.

  4. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, M H; Hvidberg, A; Juul, A

    1995-01-01

    In the present study, we 1) determined whether the impaired spontaneous 24-h GH secretion as well as the blunted GH response to provocative testing in obese subjects are persistent disorders or transient defects reversed with weight loss and 2) investigated 24-h urinary GH excretion and basal...... levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9...... reversible defects in 24-h spontaneous GH release profiles, basal IGF-I levels, and the IGF-I/IGFBP-3 molar ratio in obese subjects. The recovery of the 24-h GH release points to an acquired transient defect rather than a persistent preexisting disorder....

  5. Understanding the multifactorial control of growth hormone release by somatotropes: lessons from comparative endocrinology.

    Science.gov (United States)

    Gahete, Manuel D; Durán-Prado, Mario; Luque, Raúl M; Martínez-Fuentes, Antonio J; Quintero, Ana; Gutiérrez-Pascual, Ester; Córdoba-Chacón, José; Malagón, María M; Gracia-Navarro, Francisco; Castaño, Justo P

    2009-04-01

    Control of postnatal growth is the main, but not the only, role for growth hormone (GH) as this hormone also contributes to regulating metabolism, reproduction, immunity, development, and osmoregulation in different species. Likely owing to this variety of group-specific functions, GH production is differentially regulated across vertebrates, with an apparent evolutionary trend to simplification, especially in the number of stimulatory factors governing substantially GH release. Thus, teleosts exhibit a multifactorial regulation of GH secretion, with a number of factors, from the newly discovered fish GH-releasing hormone (GHRH) to pituitary adenylate cyclase-activating peptide (PACAP) but also gonadotropin-releasing hormone, dopamine, corticotropin-releasing hormone, and somatostatin(s) directly controlling somatotropes. In amphibians and reptiles, GH secretion is primarily stimulated by the major hypothalamic peptides GHRH and PACAP and inhibited by somatostatin(s), while other factors (ghrelin, thyrotropin-releasing hormone) also influence GH release. Finally, in birds and mammals, primary control of GH secretion is exerted by a dual interplay between GHRH and somatostatin. In addition, somatotrope function is modulated by additional hypothalamic and peripheral factors (e.g., ghrelin, leptin, insulin-like growth factor-I), which together enable a balanced integration of feedback signals related to processes in which GH plays a relevant regulatory role, such as metabolic and energy status, reproductive, and immune function. Interestingly, in contrast to the high number of stimulatory factors impinging upon somatotropes, somatostatin(s) stand(s) as the main primary inhibitory regulator(s) for this cell type.

  6. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33. Methods: Psoriasis and normal skin biopsy samples were obtained from three ...

  7. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Sent for review: 28 July 2017. Revised accepted: 27 October 2017. Abstract. Purpose: To determine the expression of corticotropin releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33.

  8. Up-regulation of corticotropin releasing hormone is associated with ...

    African Journals Online (AJOL)

    Purpose: To determine the expression of corticotropin releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33. Methods: Psoriasis and normal skin biopsy samples were obtained from three ...

  9. Suppression of androgen production by D-tryptophan-6-luteinizing hormone-releasing hormone in man.

    Science.gov (United States)

    Tolis, G; Mehta, A; Comaru-Schally, A M; Schally, A V

    1981-01-01

    Four male transsexual subjects were given a superactive luteinizing hormone-releasing hormone (LHRH) analogue, D-tryptophan-6-LHRH at daily doses of 100 micrograms for 3--6 mo. A decrease in beard growth, acne, and erectile potency was noted; the latter was documented objectively with the recordings of nocturnal penile tumescence episodes. Plasma testosterone and dihydrotestosterone levels fell to castrate values; basal prolactin and luteinizing hormone levels showed a small decline, whereas the acutely releasable luteinizing hormone was significantly suppressed. A rise of plasma testosterone from castrate to normal levels was demonstrable with the use of human chorionic gonadotropin. Discontinuation of treatment led to a normalization of erectile potency and plasma testosterone. The suppression of Leydig cell function by D-tryptophan-6-LHRH might have wide application in reproductive biology and in endocrine-dependent neoplasia (where it could replace surgical castration). PMID:6456277

  10. Sleep in mice with nonfunctional growth hormone-releasing hormone receptors.

    Science.gov (United States)

    Obal, Ferenc; Alt, Jeremiah; Taishi, Ping; Gardi, Janos; Krueger, James M

    2003-01-01

    The role of the somatotropic axis in sleep regulation was studied by using the lit/lit mouse with nonfunctional growth hormone (GH)-releasing hormone (GHRH) receptors (GHRH-Rs) and control heterozygous C57BL/6J mice, which have a normal phenotype. During the light period, the lit/lit mice displayed significantly less spontaneous rapid eye movement sleep (REMS) and non-REMS (NREMS) than the controls. Intraperitoneal injection of GHRH (50 microg/kg) failed to promote sleep in the lit/lit mice, whereas it enhanced NREMS in the heterozygous mice. Subcutaneous infusion of GH replacement stimulated weight gain, increased the concentration of plasma insulin-like growth factor-1 (IGF-1), and normalized REMS, but failed to restore normal NREMS in the lit/lit mice. The NREMS response to a 4-h sleep deprivation was attenuated in the lit/lit mice. In control mice, intraperitoneal injection of ghrelin (400 microg/kg) elicited GH secretion and promoted NREMS, and intraperitoneal administration of the somatostatin analog octretotide (Oct, 200 microg/kg) inhibited sleep. In contrast, these responses were missing in the lit/lit mice. The results suggest that GH promotes REMS whereas GHRH stimulates NREMS via central GHRH-Rs and that GHRH is involved in the mediation of the sleep effects of ghrelin and somatostatin.

  11. HORMONE THERAPY WITH USAGE OF AGONISTS AND ANTAGONISTS OF LUTEINIZING HORMONE RELEASING HORMONE IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    K. M. Nyushko

    2014-01-01

    Full Text Available Prostate cancer (PC is one of the most actual problems of modern oncourology. Hormone therapy (HT using medical castration is the main method of treatment of patients with metastatic PC. HT with usage of the new class of drugs that block the receptors for luteinizing hormone releasing hormone (LHRH is a promising and effective method of castration therapy that has a number of significant advantages over the use of analogues LHRH. This article presents areview of studies that compared the effectiveness and side effects of HT using antagonists and analogues LHRH.

  12. Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro.

    Science.gov (United States)

    Wagner, U; Wahle, M; Moritz, F; Wagner, U; Häntzschel, H; Baerwald, C G O

    2006-02-01

    To investigate whether polymorphisms in the corticotrophin-releasing hormone (CRH) promoter are associated with altered CRH gene regulation, we studied the reactivity of three recently described promoter variants in vitro. The 3625 bp variants A1B1, A2B1 and A2B2 of the human CRH promoter were cloned in the 5' region to a luciferase reporter gene and transiently transfected into both mouse anterior pituitary cells AtT-20D16vF2 and pheochromocytoma cells PC12. Incubation with 8-Br-cAMP alone or in combination with cytokines significantly enhanced the promoter activity in both cell lines studied by up to 22-fold. However, dexamethasone antagonised cAMP effects on CRH expression in AtT-20 cells while showing no effect on PC12 cells, indicating that tissue-specific factors play a crucial role. Among the haplotypes studied, A1B1 exhibited the greatest reactivity on various stimuli. Electric mobility shift assay (EMSA) was performed to study whether the described polymorphic nucleotide sequences in the 5' region of the hCRH gene interfere with binding of nuclear proteins. A specific DNA protein complex was detected at position -2353 bp for the wild type sequence only, possibly interfering with a binding site for the activating transcription factor 6 (ATF6). Taken together, this is the first study to demonstrate that CRH promoter reactivity varies between the compound promoter alleles.

  13. Mathematical modeling of gonadotropin-releasing hormone signaling.

    Science.gov (United States)

    Pratap, Amitesh; Garner, Kathryn L; Voliotis, Margaritis; Tsaneva-Atanasova, Krasimira; McArdle, Craig A

    2017-07-05

    Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are G q -coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; Vandekerckhove, P.; Lilford, R.; van der Veen, F.

    2000-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in

  15. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone

    DEFF Research Database (Denmark)

    Asa, S L; Kovacs, K; Stefaneanu, L

    1992-01-01

    It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituitary...

  16. The Effect of Lupinus albus on Growth Performance, Body Composition and Satiety Hormones of Male Pigs Immunized against Gonadotrophin Releasing Factor.

    Science.gov (United States)

    Moore, Karen; Mullan, Bruce; Kim, Jae Cheol; Dunshea, Frank

    2017-03-02

    Two hundred and ninety four pigs were used with the aim to develop a dietary management strategy using Lupinus albus L. (albus lupins) to reduce the increase in feed intake and subsequent increase in carcass fatness in pigs immunized against gonadotrophin releasing factor (immunocastrates; IC males) and entire male pigs in the late finishing stage. From day (d) 0 to 28, IC males fed the control diet grew faster (p = 0.009) than entire males fed the control diet but there was no difference in growth rate between sexes for pigs fed albus lupins for 14 days pre-slaughter (Albus 14) or pigs fed albus lupins for 28 days pre-slaughter (Albus 28). From d 15 to 28, IC males receiving the Albus 14 diet grew more slowly (p Albus 14 diet. From d 15 to 28 (p Albus 14 and Albus 28 diet. Immunocastrates had a lower backfat when fed either Albus 14 or Albus 28 compared to the control diet, although there was no difference between diets for entire males. There was also a trend for pigs on the Albus 14 and Albus 28 diets to have a higher lean deposition (p = 0.055) and a lower fat deposition (p = 0.056) compared to the pigs on the control diet. Pigs fed the Albus 28 diet had a lower plasma ghrelin concentration compared to pigs fed the Albus 14 or the control diet (p = 0.002). Pigs fed the Albus 28 diet had a higher peptide YY concentration than those fed the control or albus 14 diet (p = 0.004). The inclusion of albus lupins at 20% in the diets of IC male pigs for either 14 or 28 days pre-slaughter was successful in reducing feed intake, body fat and backfat to similar levels of entire males. However, the growth rate of the IC male pigs was impacted more than would be desirable.

  17. Development of gonadotropin-releasing hormone systems in the male African catfish, Clarias gariepinus

    NARCIS (Netherlands)

    Dubois, E.A.

    2001-01-01

    Reproductive processes are mainly regulated by the brain-pituitary-gonad axis (BPG-axis). Gonadotropin-releasing hormone (GnRH) neurons localized in the brain release their hormone GnRH, which allows the release of gonadotropic hormone by gonadotropic cells in the pituitary. Gonadotropic

  18. The Effect of Lupinus albus on Growth Performance, Body Composition and Satiety Hormones of Male Pigs Immunized against Gonadotrophin Releasing Factor

    Directory of Open Access Journals (Sweden)

    Karen Moore

    2017-03-01

    Full Text Available Two hundred and ninety four pigs were used with the aim to develop a dietary management strategy using Lupinus albus L. (albus lupins to reduce the increase in feed intake and subsequent increase in carcass fatness in pigs immunized against gonadotrophin releasing factor (immunocastrates; IC males and entire male pigs in the late finishing stage. From day (d 0 to 28, IC males fed the control diet grew faster (p = 0.009 than entire males fed the control diet but there was no difference in growth rate between sexes for pigs fed albus lupins for 14 days pre-slaughter (Albus 14 or pigs fed albus lupins for 28 days pre-slaughter (Albus 28. From d 15 to 28, IC males receiving the Albus 14 diet grew more slowly (p < 0.001 than entire males receiving the Albus 14 diet. From d 15 to 28 (p < 0.001, IC males fed the control diet ate more feed than entire males fed the control diet, although there was no difference between sexes in feed intake of the Albus 14 and Albus 28 diet. Immunocastrates had a lower backfat when fed either Albus 14 or Albus 28 compared to the control diet, although there was no difference between diets for entire males. There was also a trend for pigs on the Albus 14 and Albus 28 diets to have a higher lean deposition (p = 0.055 and a lower fat deposition (p = 0.056 compared to the pigs on the control diet. Pigs fed the Albus 28 diet had a lower plasma ghrelin concentration compared to pigs fed the Albus 14 or the control diet (p = 0.002. Pigs fed the Albus 28 diet had a higher peptide YY concentration than those fed the control or albus 14 diet (p = 0.004. The inclusion of albus lupins at 20% in the diets of IC male pigs for either 14 or 28 days pre-slaughter was successful in reducing feed intake, body fat and backfat to similar levels of entire males. However, the growth rate of the IC male pigs was impacted more than would be desirable.

  19. Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release.

    Science.gov (United States)

    Molnár, Zsolt; Pálföldi, Regina; László, Anna; Radács, Marianna; Sepp, Krisztián; Hausinger, Péter; Tiszlavicz, László; Valkusz, Zsuzsanna; Gálfi, Márta

    2015-08-01

    Many environmental chemicals and pesticides have been found to alter neuroendocrine communication in exposed biological objects. The environmental loads have primary and secondary effects that can alter the homeostatic regulation potential. Since it is difficult to avoid human exposition, a potentially important area of research to develop in vivo and in vitro experimental models. In this context, the primary aim of this study was to demonstrate the effects of chlorobenzenes on adrenocorticotrophic hormone (ACTH) release. In our experimental study, male Wistar rats were exposed to 0.1, 1.0 and 10 μg/b.w. (body weight)kg of 1,2,4- trichlorobenzene and hexachlorobenzene (ClB) mix via gastric tube for 30, 60 or 90 days. At the endpoints of the experiment blood samples were taken and animals were decapitated. Primary, monolayer adenohypophysis cell cultures were prepared by enzymatic and mechanical digestion. The ACTH hormone content in serum and supernatant media was measured by immuno-chemiluminescence assay. The Mg(2+)-dependent ATPase activity was determined by modified method of Martin and Dotty. Significant differences were detected in the hormone release between the control and treated groups. The hormone release was enhanced characteristically in exposed groups depending upon the dose and duration of exposure. The Mg(2+)-ATPase activity enhanced after chronic and subtoxic ClB exposition. Light microscopy revealed that the adenohypophysis seemed to be more abundant. Results indicate that Wistar rats exposed to subtoxic ClB have direct and indirect effects on hypothalamus-hypophysis-adrenal axis. Copyright © 2015. Published by Elsevier B.V.

  20. Luteinizing hormone responses to luteinizing hormone releasing hormone, and growth hormone and cortisol responses to insulin induced hypoglycaemia in functional secondary amenorrhoea.

    Science.gov (United States)

    Hirvonen, E; Seppälä, M; Karonen, S L; Adlercreutz, H

    1977-02-01

    Luteinizing hormone (LH) responses to luteinizing hormone releasing hormone (LHRH), and growth hormone (GH) and cortisol responses to insulin induced hypoglycaemia were studied in 56 women classified into 4 distinct groups of functional secondary amenorrhoea. The groups were: I, self-induced weight reduction (20 patients); II, post pill amenorrhoea (14 patients); III, anorexia nervosa (10 patients); and IV, idiopathic secondary amenorrhoea (12 patients). Only patients with no overlapping anamnestic factors were included. Group I patients had the most heavily impaired LHRH-LH responses, and the GH response to hypoglycaemia was smaller than in other groups. Cortisol responses were normal. Group II patients showed blunted LH responses and normal GH and cortisol responses. Group III patients showed normal or exaggerated LH responses in the recovery phase of anorexia nervosa, while those two patients who were in the static phase of the illness had impaired responses. GH responses varied greatly. Group IV patients had normal basal levels of LH and normal LH, GH and cortisol responses. The restoration of LH response is not solely correlated to body mass, since patients recovering from anorexia nervosa showed greater LHRH-LH responses with nutritional rehabilitation at 76% of ideal body weight than patients with self-induced weight reduction at 87% of ideal body weight. In idiopathic amenorrhoea the hypothalamic pituitary axis seems to be practically intact. The function of hypothalamic-pituitary axis may be impaired selectively in functional amenorrhoea. Corticotrophin releasing hormone function remains intact, and GH-response may be impaired or normal independently of the LH-response to LHRH. In self-induced weight reduction both functions were impaired. These tests are easily carried out with out-patients, and they give more information about the functional state of hypothalamic-pituitary axis than basal analyses of hypothalamic-pituitary axis than basal analyses of

  1. 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...... (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...

  2. Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer

    DEFF Research Database (Denmark)

    Østergren, Peter Busch; Kistorp, Caroline; Fode, Mikkel

    2017-01-01

    levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin. MATERIALS AND METHODS: In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev...

  3. The neuropeptide Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in the earthworm: Eisenia foetida.

    Science.gov (United States)

    Luis Quintanar, J; Gutiérrez-García, Karina; Castillo-Hernández, Luis

    2011-12-01

    We investigated whether the Gonadotropin-releasing hormone affects the spontaneous muscular contraction in the earthworm Eisenia foetida. In addition, we investigated the presence of Gonadotropin-releasing hormone receptor in ventral nerve cord by immunohistochemistry and polymerase chain reaction. Gonadotropin-releasing hormone induced a significant increase on both amplitude and muscular tone and decrease in the frequency of spontaneous muscular contraction. We found the presence of immunoreactive material to Gonadotropin-releasing hormone receptor in the ventral nerve cord, likewise the Gonadotropin-releasing hormone receptor mRNA expression. In conclusion, the Gonadotropin-releasing hormone modifies the spontaneous muscular contraction in E. foetida and these effects can be due to the activation of the Gonadotropin-releasing hormone receptor.

  4. 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.

  5. In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue.

    Science.gov (United States)

    Moradi, Shayli Varasteh; Varamini, Pegah; Steyn, Frederik; Toth, Istvan

    2015-11-10

    In the current study, the efficacy and pharmacokinetic profile of lactose-conjugated luteinizing hormone releasing hormone (LHRH) was examined following oral administration in male rats. A rapid and sensitive liquid chromatography/mass spectrometry technique was developed and applied for measuring the concentration of lactose[Q(1)][w(6)]LHRH (compound 1) in rat plasma in order to allow measurement of pharmacokinetic parameters. LH release was evaluated using a sandwich ELISA. Maximum serum concentration (Cmax = 0.11 μg/ml) was reached at 2h (Tmax) following oral administration of the compound at 10mg/kg. The half-life was determined to be 2.6h. The absolute bioavailability of the orally administered compound was found to be 14%, which was a remarkable improvement compared to zero-to-low oral bioavailability of the native peptide. Compound 1 was effective in stimulating LH release at 20mg/kg after oral administration. The method was validated at a linear range of 0.01-20.0 μg/ml and a correlation coefficient of r(2) ≥ 0.999. The accuracy and precision values showed the reliability and reproducibility of the method for evaluation of the pharmacokinetic parameters. These findings showed that the lactose derivative of LHRH has a therapeutic potential to be further developed as an orally active therapeutics for the treatment of hormone-dependent diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Hormonal Factors and Disturbances in Eating Disorders.

    Science.gov (United States)

    Culbert, Kristen M; Racine, Sarah E; Klump, Kelly L

    2016-07-01

    This review summarizes the current state of the literature regarding hormonal correlates of, and etiologic influences on, eating pathology. Several hormones (e.g., ghrelin, CCK, GLP-1, PYY, leptin, oxytocin, cortisol) are disrupted during the ill state of eating disorders and likely contribute to the maintenance of core symptoms (e.g., dietary restriction, binge eating) and/or co-occurring features (e.g., mood symptoms, attentional biases). Some of these hormones (e.g., ghrelin, cortisol) may also be related to eating pathology via links with psychological stress. Despite these effects, the role of hormonal factors in the etiology of eating disorders remains unknown. The strongest evidence for etiologic effects has emerged for ovarian hormones, as changes in ovarian hormones predict changes in phenotypic and genetic influences on disordered eating. Future studies would benefit from utilizing etiologically informative designs (e.g., high risk, behavioral genetic) and continuing to explore factors (e.g., psychological, neural responsivity) that may impact hormonal influences on eating pathology.

  7. Human growth hormone and gonadotropin releasing hormone analog combination therapy increases predicted height in short normal girls.

    Science.gov (United States)

    Maniati-Christidi, M; Livadas, S; Voutetakis, A; Tolis, G; Dacou-Voutetakis, C

    2003-01-01

    The "short normal" child constitutes a real challenge for the pediatric endocrinologist. In a subgroup of short normal children, puberty starts at a normal age but with low height, and hence, the final height is expected to be quite compromised. Efforts to improve the outcome in this group have been made in the past with equivocal results. We present the growth data of 8 short girls with normal growth hormone values on provocative testing and low height at puberty initiation. At intervention the height and the stage of puberty were 129.3 +/- 5 cm and II to III, respectively, and the predicted height was 148.8 +/- 2.6 cm. Gonadotropin releasing hormone analog, triptorelin (3.6 +/- 0.5 microg/kg/day) and growth hormone (0.5 IU/kg/week) were used in different sequential order and simultaneously in each child. The mean total treatment period was 47.6 +/- 11.2 months. The mean predicted and the mean final height in the total group were 148.8 +/- 2.6 and 154.5 +/- 3.6 cm, respectively (p:0.028). The final height did not differ from the target height (154.8 +/- 8 cm versus 154.5 +/- 3.6 cm), while in 4 children, the final height was greater than the target height. The height gain (delta Final height - Predicted height) was 5.7 +/- 1.3 cm. If we analyze separately the girls in whom growth hormone was started first and gonadotropin releasing hormone analog followed versus those who started the analog first, the delta Final height - Predicted height was 8 +/- 3 cm in the former and 4.8 +/- 3.1 cm in the latter (p:0.03). It seemed that the difference was accounted for by duration of growth hormone therapy (51.3 +/- 10.6 months versus 28.6 +/- 10.6 months) (p:0.026), rather than by other factors. In conclusion, under the conditions of the present study, the combination of puberty arrest and growth hormone therapy significantly improved predicted height. The most significant determinant of the height gain was the duration of growth hormone therapy.

  8. Receptors for thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormones in the macaque uterus: effects of long-term sex hormone treatment.

    Science.gov (United States)

    Hulchiy, Mariana; Zhang, Hua; Cline, J Mark; Hirschberg, Angelica Lindén; Sahlin, Lena

    2012-11-01

    Thyroid gland dysfunction is associated with menstrual cycle disturbances, infertility, and increased risk of miscarriage, but the mechanisms are poorly understood. However, little is known about the regulation of these receptors in the uterus. The aim of this study was to determine the effects of long-term treatment with steroid hormones on the expression, distribution, and regulation of the receptors for thyrotropin-releasing hormone (TRHR) and thyroid-stimulating hormone (TSHR), thyroid hormone receptor α1/α2 (THRα1/α2), and THRβ1 in the uterus of surgically menopausal monkeys. Eighty-eight cynomolgus macaques were ovariectomized and treated orally with conjugated equine estrogens (CEE; n = 20), a combination of CEE and medroxyprogesterone acetate (MPA; n = 20), or tibolone (n = 28) for 2 years. The control group (OvxC; n = 20) received no treatment. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in luminal epithelium, glands, stroma, and myometrium of the uterus. Immunostaining of TRHR, TSHR, and THRs was detected in all uterine compartments. Epithelial immunostaining of TRHR was down-regulated in the CEE + MPA group, whereas in stroma, both TRHR and TSHR were increased by CEE + MPA treatment as compared with OvxC. TRHR immunoreactivity was up-regulated, but THRα and THRβ were down-regulated, in the myometrium of the CEE and CEE + MPA groups. The thyroid-stimulating hormone level was higher in the CEE and tibolone groups as compared with OvxC, but the level of free thyroxin did not differ between groups. All receptors involved in thyroid hormone function are expressed in monkey uterus, and they are all regulated by long-term steroid hormone treatment. These findings suggest that there is a possibility of direct actions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone on uterine function.

  9. Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones.

    Science.gov (United States)

    Wang, Lixin; Goebel-Stengel, Miriam; Yuan, Pu-Qing; Stengel, Andreas; Taché, Yvette

    2017-01-01

    Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4-6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting

  10. Analysis of the stress response in rats trained in the water-maze: differential expression of corticotropin-releasing hormone, CRH-R1, glucocorticoid receptors and brain-derived neurotrophic factor in limbic regions.

    Science.gov (United States)

    Aguilar-Valles, Argel; Sánchez, Edith; de Gortari, Patricia; Balderas, Israela; Ramírez-Amaya, Víctor; Bermúdez-Rattoni, Federico; Joseph-Bravo, Patricia

    2005-01-01

    Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses. Different types of stress activate the CRH system; in hypothalamus, CRH expression and release are increased by physical or psychological stressors while in amygdala, preferentially by psychological stress. Learning and memory processes are modulated by glucocorticoids and stress at different levels. To characterize the kind of stress provoked by a hippocampal-dependent task such as spatial learning, we compared the expression profile of glucocorticoid receptor (GR), pro-CRH and CRH-R1 mRNAs (analyzed by RT-PCR), in amygdala, hippocampus and hypothalamus and quantified serum corticosterone levels by radioimmunoassay at different stages of training. mRNA levels of brain-derived neurotrophic factor (BDNF) were also quantified due to its prominent role in learning and memory processes. Male Wistar rats trained for 1, 3 or 5 days in the Morris water-maze (10 trials/day) were sacrificed 5-60 min the after last trial. A strong stress response occurred at day one in both yoked and trained animals (increased corticosterone and hypothalamic pro-CRH and CRH-R1 mRNA levels); changes gradually diminished as the test progressed. In amygdala, pro-CRH mRNA levels decreased while those of BDNF augmented when stress was highest, in yoked and trained animals. Hippocampi, of both yoked and trained groups, had decreased levels of GR mRNA on days 1 and 3, normalizing by day 5, while those of pro-CRH and CRH-R1 increased after the 3rd day. Increased gene expression, specifically due to spatial learning, occurred only for hippocampal BDNF since day 3. These results show that the Morris water-maze paradigm induces a strong stress response that is gradually attenuated. Inhibition of CRH expression in amygdala suggests that the stress inflicted is of physical but not of psychological nature and could lead to reduced fear or anxiety.

  11. Psychoneuromedulator role of corticotrophin releasing hormone in PCOS

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2016-10-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndromes. Noradrenalin (NA, corticotrophin releasing hormone (CRH and nerve growth factor (NGF are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-ovarian (HPO axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system over activity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case-control study was conducted in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in the September of 2011. 170 women participated in this study. The diagnosis of PCOS was made according to the joint criteria of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine (ESHRE/ASRM. All women have 20-40 years of age and body mass index (BMI of less than 28. Demographic questionnaire was used in this study and blood sample was obtained from all participants before 8AM. All analysis was done in SPSS software, version 19 (IBM SPSS, Armonk, NY, USA. P-value less than 0.05 considered as significant level. Results: Serum levels of CRH and NGF in patients with polycystic ovary was significantly lower than the control group (P< 0.001. This reduction can disrupt two neural axes: the sympathetic nervous system (SAS and hypothalamus-pituitary-adrenal (HPA. These axes have a fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and qualitative characteristics of the population studied, the results of which are reported in the regression

  12. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, M H; Hvidberg, A; Juul, A

    1995-01-01

    In the present study, we 1) determined whether the impaired spontaneous 24-h GH secretion as well as the blunted GH response to provocative testing in obese subjects are persistent disorders or transient defects reversed with weight loss and 2) investigated 24-h urinary GH excretion and basal...... levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9...... reduced weight obese subjects after a diet-induced average weight loss of 30.3 +/- 4.6 kg. Twenty-four-hour spontaneous GH secretion was estimated by obtaining 3240 integrated 20-min blood samples using a constant blood withdrawal technique and computerized algorithms. Body composition was determined...

  13. Goserelin acetate implant: a depot luteinizing hormone-releasing hormone analog for advanced prostate cancer.

    Science.gov (United States)

    Goldspiel, B R; Kohler, D R

    1991-01-01

    Goserelin acetate implant is a newly approved depot formulation of a luteinizing hormone-releasing hormone (LHRH) agonist indicated for palliation of advanced prostate cancer. LHRH superagonists suppress gonadotropin release from the pituitary gland by causing down-regulation of receptors. The sustained-release dosage form contains goserelin acetate dispersed in a biodegradable copolymer matrix and is designed to release active drug over 28 days. Pharmacokinetic studies have demonstrated that, despite nonzero order release of goserelin from the matrix, goserelin acetate implant maintains serum concentrations of testosterone in the range normally found in castrated men (less than 2 nmol/L) throughout the recommended 28-day dosing interval. Response rates similar to those for orchiectomy and estrogen administration have been demonstrated. Combination therapy with either diethylstilbestrol or flutamide has produced favorable results, although the major advantage appears to be a reduction in the tumor flare seen during the first week of LHRH agonist therapy rather than an increase in response rate or survival. Adverse effects are similar to other LHRH agonists and include tumor flare during the first week of therapy, decreased libido, decreased erectile potency, hot flashes, and gynecomastia. In combination with flutamide, additional adverse effects include diarrhea, nausea, vomiting, and elevated hepatic aminotransferases, all of which can be attributed to flutamide administration. Local reactions are minimal; however, some patients require a local anesthetic before goserelin acetate implant injection. The recommended dose is 3.6 mg administered subcutaneously into the upper abdominal wall every 28 days. The average wholesale cost is approximately +320 per month. Formulary addition is recommended.

  14. The Highly Conserved Gonadotropin-Releasing Hormone-2 Form Acts as a Melatonin-Releasing Factor in the Pineal of a Teleost Fish, the European Sea Bass Dicentrarchus labrax

    National Research Council Canada - National Science Library

    Servili, Arianna; Lethimonier, Christèle; Lareyre, Jean-Jacques; López-Olmeda, José Fernando; Sánchez-Vázquez, Francisco Javier; Kah, Olivier; Muñoz-Cueto, José Antonio

    2010-01-01

    .... In addition, in many teleost fish, there is a third gene called GnRH-3. If the main function of GnRH-1 is unambiguously to stimulate gonadotropin release, the other two GnRH forms still lack clear functions...

  15. Thyrotropin-releasing hormone (TRH) in the cerebellum.

    Science.gov (United States)

    Shibusawa, Nobuyuki; Hashimoto, Koshi; Yamada, Masanobu

    2008-01-01

    Thyrotropin-releasing hormone (TRH) was originally isolated from the hypothalamus. Besides controlling the secretion of TSH from the anterior pituitary, this tripeptide is widely distributed in the central nervous system and regarded as a neurotransmitter or modulator of neuronal activities in extrahypothalamic regions, including the cerebellum. TRH has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation. TRH controls energy homeostasis mainly through its hypophysiotropic actions to regulate circulating thyroid hormone levels. Recent investigations have revealed that TRH production is regulated directly at the transcriptional level by leptin, one of the adipocytokines that plays a critical role in feeding and energy expenditure. The improvement of ataxic gait is one of the important pharmacological properties of TRH. In the cerebellum, cyclic GMP has been shown to be involved in the effects of TRH. TRH knockout mice show characteristic phenotypes of tertiary hypothyroidism, but no morphological changes in their cerebellum. Further analysis of TRH-deficient mice revealed that the expression of PFTAIRE protein kinase1 (PFTK1), a cdc2-related kinase, in the cerebellum was induced by TRH through the NO-cGMP pathway. The antiataxic effect of TRH and TRH analogs has been investigated in rolling mouse Nagoya (RMN) or 3-acetylpyridine treated rats, which are regarded as a model of human cerebellar degenerative disease. TRH and TRH analogs are promising clinical therapeutic agents for inducing arousal effects, amelioration of mental depression, and improvement of cerebellar ataxia.

  16. 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...

  17. Thyroid hormones regulate levels of thyrotropin-releasing-hormone mRNA in the paraventricular nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Koller, K.J.; Wolff, R.S.; Warden, M.K.; Zoeller, R.T.

    1987-10-01

    Cellular levels of messenger RNA encoding thyrotropin-releasing hormone (TRH) were measured in the paraventricular nucleus of the hypothalamus and the reticular nucleus of the thalamus in male rats after chemical thyroidectomy and thyroid hormone, replacement. TRH mRNA levels were measured by quantitative in situ hybridization histochemistry using a /sup 35/S-labeled synthetic 48-base oligodeoxynucleotide probe and quantitative autoradiography. Chemical thyroidectomy, produced by the administration of 6-(n-propyl)-2-thiouracil (PrSur), reduced plasma thyroxine below detection limits and significantly increased TRH mRNA in the paraventricular nucleus. Treatments with exogenous L-triiodothyronine (T/sub 3/) reduced TRH mRNA to the same level in both hypothyroid and euthyroid animals. Neither PrSur treatment nor T/sub 3/ replacement influenced TRH mRNA levels in the reticular nucleus of the thalamus. Blot hybridization analysis of electrophoretically fractionated total RNA from pituitaries of these animals indicated that thyrotropin-..beta.. mRNA levels were elevated after thyroidectomy and reduced by T/sub 3/ treatment, showing that the pituitary-thyroid axis was indeed stimulated by PrSur treatment. These results suggest that thyroid hormones are involved, either directly or indirectly, in regulating the biosynthesis of TRH in the thyrotropic center of the hypothalamus.

  18. Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus.

    Directory of Open Access Journals (Sweden)

    Guillaume Osterstock

    2010-02-01

    Full Text Available Ghrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate.Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders.

  19. Circadian and sleep-dependent regulation of hormone release in humans

    Science.gov (United States)

    Czeisler, C. A.; Klerman, E. B.

    1999-01-01

    Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian

  20. Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

    Science.gov (United States)

    Ignacio, Daniele Leão; da S. Silvestre, Diego H.; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

  1. Pituitary immediate release pools of growth hormone and prolactin are preferentially refilled by new rather than stored hormone.

    Science.gov (United States)

    Stachura, M E; Tyler, J M; Kent, P G

    1989-07-01

    Pituitary stores of rat GH (rGH) and PRL (rPRL) are divisible into immediately releasable and more stable compartments representing either compartmentalized hormone within individual cells of a homogeneous population or responses of specialized cell subsets in a functionally heterogeneous population. In addition, newly synthesized rGH and rPRL can be processed either into intracellular storage or toward direct release. Fractional assignment of new hormone to these two paths can be influenced in the somatotroph by GHRH and may also represent either intracellular processes or functional heterogeneity of cells. We investigated the source, newly synthesized or stored, of hormone refilling the somatotroph and lactotroph immediately releasable pools (IRP) after their discharge by 21 mM potassium ion, 1 mM (Bu)2cAMP, 3 nM human GHRH-44, or 3 microM prostaglandin E1. Experiments were performed using perifused pituitary fragments exposed sequentially to [14C]- and [3H]leucine in association with stimulation by two 30-min pulses of the same secretagogue. Therefore, only [14C]hormone was available for release by the first stimulus, whereas both [14C]- and [3H]hormone were available for release by the second stimulus. Analysis was by specific immunoprecipitation. The first episode of stored [14C]rGH release exceeded the second episode of stored [14C]rGH release in response to each secretagogue. However, release of newly synthesized [3H]rGH in response to the second episode of stimulation exceeded the simultaneous release of stored [14C]rGH while matching or exceeding the [14C]rGH release that had occurred in the same experiment in response to the first episode of stimulation. Refilling both GH and PRL IRP stores drew primarily upon newly synthesized hormone, but with different secretagogue-specific patterns. These data confirm differential handling of new and stored rGH and rPRL within the pituitary. They are consistent with either (1) the enhanced shunting of newly

  2. Divergent activity of the gonadotropin-releasing hormone receptor gene promoter among genetic lines of pigs is partially conferred by nuclear factor (NF)-B, specificity protein (SP)1-like and GATA-4 binding sites.

    Science.gov (United States)

    McDonald, Emily A; Smith, Jacqueline E; Cederberg, Rebecca A; White, Brett R

    2016-06-29

    Binding of gonadotropin-releasing hormone (GnRH) to its receptor (GnRHR) on gonadotropes within the anterior pituitary gland is essential to reproduction. In pigs, the GnRHR gene is also located near a genetic marker for ovulation rate, a primary determinant of prolificacy. We hypothesized that pituitary expression of the GnRHR gene is alternatively regulated in genetic strains with elevated ovulation rates (Chinese Meishan and Nebraska Index) vs. standard white crossbred swine (Control). Luciferase reporter vectors containing 5118 bp of GnRHR gene promoter from either the Control, Index or Meishan swine lines were generated. Transient transfection of line-specific, full length, deletion and mutation constructs into gonadotrope-derived αT3-1 cells were performed to compare promoter activity and identify regions necessary for divergent regulation of the porcine GnRHR gene. Additionally, transcription factors that bind the GnRHR promoter from each line were identified with electrophoretic mobility shift assays (EMSA). Dramatic differences in luciferase activity among Control, Index and Meishan promoters (19-, 27- and 49-fold over promoterless control, respectively; P Index promoters. Transient transfection of vectors containing block replacement mutations of either the GATA-4 or NF-κB binding sites within the context of their native promoters resulted in a 50 and 60 % reduction of luciferase activity, respectively (P Index promoters resulted in binding of the p52 and p65 subunits of NF-κB and a specificity protein 1 (SP1)-like factor (-1235) as well as GATA-4 (-845). Vectors containing the full-length Meishan promoter harboring individual mutations spanning these regions reduced luciferase activity by 25 and 20 %, respectively, compared to native sequence (P Index promoters in αT3-1 cells is partially due to three single nucleotide polymorphisms resulting in the unique binding of GATA-4 (-1690), the p52/p65 subunits of NF-kB in combination with a SP1

  3. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

    Science.gov (United States)

    Al-Inany, Hesham G; Youssef, Mohamed Afm; Aboulghar, Mohamed; Broekmans, Frank; Sterrenburg, Monique; Smit, Janine; Abou-Setta, Ahmed M

    2011-05-11

    Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-estrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotropin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimes have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006. To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycle We performed electronic searches of major databases, for example Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE (from 1987 to April 2010); and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). A date limited search of Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL

  4. The chicken pituitary-specific transcription factor Pit-1 is involved in the hypothalamic regulation of pituitary hormones

    NARCIS (Netherlands)

    As, van P.; Janssens, K.; Pals, K.; Groef, De B.; Onagbesan, O.M.; Bruggeman, V.; Darras, V.M.; Denef, C.; Decuypere, E.

    2006-01-01

    Pit-1 is a pituitary-specific POU-domain DNA binding factor, which binds to and trans-activates promoters of growth hormone- (GH), prolactin- (PRL) and thyroid stimulating hormone-beta- (TSHbeta) encoding genes. Thyrotropin-releasing hormone (TRH) is located in the hypothalamus and stimulates TSH,

  5. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.

    Science.gov (United States)

    Tolis, G; Ackman, D; Stellos, A; Mehta, A; Labrie, F; Fazekas, A T; Comaru-Schally, A M; Schally, A V

    1982-01-01

    Ten patients with prostatic carcinoma--six with stage C and four with stage D disease--were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6]LH-RH was given subcutaneously once daily at a dose of 100 microgram and [D-Ser(But)6]des-GlyNH2(10)-LH-RH ethylamide (HOE 766) was given subcutaneously (50 microgram once daily) or intranasally (500 microgram twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for greater than 12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogous of LH-RH may be used to assess the responsiveness of patients to surgical castration. Long-term administration of LH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma. Images PMID:6461861

  6. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH).

    Science.gov (United States)

    Obayemi, J D; Dozie-Nwachukwu, S; Danyuo, Y; Odusanya, O S; Anuku, N; Malatesta, K; Soboyejo, W O

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV-Visible (UV-Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. [Effectiveness of skin icing for reducing pain associated with luteinizing hormone-releasing hormone agonist injection].

    Science.gov (United States)

    Nomura, Tsunehisa; Tsunoda, Kazuko; Ohta, Satoko; Doi, Katsumi; Miyoshi, Kazuya; Hasegawa, Yasuhisa; Mizutani, Masami

    2014-02-01

    We evaluated the effect of using the cooling method on pain at the site of luteinizing hormone-releasing hormone(LH-RH) agonist injection in 181 prostate cancer or premenopausal breast cancer patients by using a numerical rating scale(NRS)and a questionnaire survey with open-ended questions. According to the NRS, 38.1% of the patients experienced a reduction in pain, 37.5% experienced no change, and 24.4% experienced an increase in pain. Therefore, use of the cooling method did not have a statistically significant effect in terms of pain reduction(p=0.123). However, on analyzing pain reduction according to the answers in the questionnaire survey, 53.2% of the patients experienced a reduction in pain, 38.5% experienced no change, and 8.3% experienced an increase in pain. These findings were different from those obtained on using the NRS. In addition, irrespective of using the cooling method, needle thickness and patient obesity strongly influenced the pain experienced. The skin icing method was effective in reducing pain at the site of LH-RH agonist injection. This method is simple, inexpensive, and safe, and is hence recommended.

  8. Redefining the gonadotrophin-releasing hormone neurone dendrite.

    Science.gov (United States)

    Campbell, R E; Suter, K J

    2010-07-01

    Gonadotrophin-releasing hormone (GnRH) neurones are the final output neurones of the complex synaptic network responsible for the central control of fertility. This scattered population of neurones has been shown to have remarkably long dendritic processes by cell-filling of GnRH neurones in situ with low-molecular weight dyes. This review focuses on how the functional significance of these long dendritic extensions is being explored through dual somatic-dendritic electrophysiological recordings, computational modelling, immunolabelling for specific channels and multiple modes of microscopy and imaging. Remarkably, recent work has discovered that GnRH neurone dendrites not only actively propagate action potentials, but also comprise the primary site of action potential initiation. These findings, along with the discovery of regionalized expression of active conductances, highlight dendrites of single GnRH neurones as being central sites of signal integration. Moreover, imaging studies have shown that the long dendrites of GnRH neurones intertwine and bundle with one another. The presence of shared synaptic input to bundling dendrites, coupled with their active properties and the increased potency of distally placed synaptic inputs, is suggestive of a novel mechanism of GnRH neurone synchronisation, a feature critical for mammalian reproduction. Together, these discoveries of the GnRH neurone dendrite structure and function are changing the way that we view the central regulation of fertility.

  9. Thyrotropin-releasing hormone (TRH) reverses hyperglycemia in rat.

    Science.gov (United States)

    Luo, LuGuang; Luo, John Z Q; Jackson, Ivor M D

    2008-09-12

    Hyperglycemia in thyrotropin-releasing hormone (TRH) null mice indicates that TRH is involved in the regulation of glucose homeostasis. Further, TRH levels in the pancreas peak during the stages of late embryonic and early neonatal beta cell development. These observations are consistent in linking TRH to islet cell proliferation and differentiation. In this study, we examined the effect of TRH administration in damaged pancreatic rat (streptozotocin, STZ) to determine whether TRH could improve damaged pancreatic beta cells function. We hypothesize that TRH is able to reverse STZ-induced hyperglycemia by increasing pancreatic islet insulin content, preventing apoptosis, and potentially induce islet regeneration. It was found that following intra-peritoneal (ip) injection, TRH (10 microg/kg body weight (bwt)) reverses STZ (65 mg/kg bwt)-induced hyperglycemia (TRH given 3 days after STZ injection). Increased circulating insulin levels and insulin content in extracted pancreas suggests that TRH reversed STZ-induced hyperglycemia through improving pancreatic islet beta cell function. Further studies show a significantly lower level of apoptosis in islets treated with TRH as well as the presence of proliferation marker nestin and Brdu, suggesting that the TRH has the potential to prevent apoptosis and stimulate islet proliferation.

  10. Corticotropin?releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation

    OpenAIRE

    Burnley, Brittney; P. Jones, Harlan

    2017-01-01

    Abstract The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin?releasing hormone (CRH) is a neuropeptide released from the hypothalamic?pituitary?adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates im...

  11. Bovine pars tuberalis secretions release growth hormone from rat pars distalis of pituitary gland.

    Science.gov (United States)

    Lafarque, Martha María; Ezquer, Marcelo; Aguado, Luis Inocencio; Oliveros, Liliana Beatriz

    2004-08-01

    The pituitary pars tuberalis (PT) is characterized by PT-specific secretory cells which have raised the possibility of an endocrine function for this portion of adenohypophysis. To investigate the effect of the secretion of bovine PT cells into culture medium on growth hormone (GH) response of dispersed pars distalis (PD) cells of rats. 48-hour culture medium of all PT cells at 1 microg of protein concentration induced the greatest GH release from PD cells. After PT cells separation on a discontinuos Percoll gradient and culturing, only the culture medium of cells from 50 and 60% Percoll strength released GH from PD cells. Therefore, cells from 50 and 60% strenght Percoll were cultured together. Only 0.2 mg protein of this culture medium was required to induce the maximal GH release from PD cells, suggesting that these cells could be responsible for producing the factor(s) which affect PD somatotrophe cells. After protein separation by 12% SDS-PAGE of this PT culture medium bands were eluted. The biological activity, measured as ng/ml of GH from PD cells, corresponded to a protein(s) of molecular weight between 45 and 66 kDal. The results indicate that there is an active proteic factor(s) secreted by the PT that acts upon PD cells to stimulate GH release and that PD could be an effector organ for some secretory product(s) of the PT.

  12. Simultaneous measurement of hormone release and secretagogue binding by individual pituitary cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P.F.; Neill, J.D.

    1987-08-01

    The quantitative relationship between receptor binding and hormone secretion at the single-cell level was investigated in the present study by combining a reverse hemolytic plaque assay for measurement of luteinizing hormone (LH) secretion from individual pituitary cells with an autoradiographic assay of /sup 125/I-labeled gonadontropin-releasing hormone (GnRH) agonist binding to the same cells. In the plaque assay, LH secretion induces complement-mediated lysis of the LH-antibody-coated erythrocytes around the gonadotropes, resulting in areas of lysis (plaques). LH release from individual gonadotropes was quantified by comparing radioimmunoassayable LH release to hemolytic area in similarly treated cohort groups of cells; plaque area was linearly related to the amount of LH secreted. Receptor autoradiography was performed using /sup 125/I-labeled GnRH-A (a superagonist analog of GnRH) both as the ligand and as the stimulant for LH release in the plaque assay. The grains appeared to represent specific and high-affinity receptors for GnRH because (i) no pituitary cells other than gonadotropes bound the labeled ligand and (ii) grain development was progressively inhibited by coincubation with increasing doses of unlabeled GnRH-A. The authors conclude that GnRH receptor number for any individual gonadotrope is a weak determinant of the amount of LH it can secrete; nevertheless, full occupancy of all its GnRH receptors is required for any gonadotrope to reach its full LH-secretory capacity. Apparently the levels of other factors comprising the steps along the secretory pathway determine the secretory capacity of an individual cell.

  13. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  14. A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH-stimulated luteinizing hormone (LH secretion

    Directory of Open Access Journals (Sweden)

    Musgrove Lois C

    2001-11-01

    Full Text Available Abstract Background Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs. These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion from cultured rat pituitary cells. Results A truncated version of RGS3 (RGS3T = RGS3 314–519 inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein. Conclusions RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino

  15. Active immunization against gonadotropin-releasing hormone : an effective tool to block the fertility axis in mammals

    NARCIS (Netherlands)

    Turkstra, Jouwert Anne

    2005-01-01

    Gonadotropin releasing hormone (GnRH) plays a pivotal role in fertility and reproduction in mammals. It induces the release of luteinising hormone (LH) en follicle stimulating hormone (FSH) from the pituitary. These hormones are responsible for gonadal steroid production and indirectly for

  16. Biosynthesis and the conjugation of magnetite nanoparticles with luteinizing hormone releasing hormone (LHRH)

    Energy Technology Data Exchange (ETDEWEB)

    Obayemi, J.D. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Materials Science and Engineering, Kwara State University, Malete, Kwara State (Nigeria); Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Danyuo, Y. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Department of Electronics and Electricals Engineering, Nigerian Turkish Nile University, Abuja (Nigeria); Odusanya, O.S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO) Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY 10453 (United States); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Malatesta, K. [Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST) Abuja, Federal Capital Territory (Nigeria); Princeton Institute of Science and Technology of Materials (PRISM), Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, NJ 08544 (United States)

    2015-01-01

    This paper presents the results of an experimental study of the biosynthesis of magnetite nanoparticles (BMNPs) with particle sizes between 10 nm and 60 nm. The biocompatible magnetic nanoparticles are produced from Magnetospirillum magneticum (M.M.) bacteria that respond to magnetic fields. M.M. bacteria were cultured and used to synthesize magnetite nanoparticles. This was done in an enriched magnetic spirillum growth medium (EMSGM) at different pH levels. The nanoparticle concentrations were characterized with UV–Visible (UV–Vis) spectroscopy, while the particle shapes were elucidated via transmission electron microscopy (TEM). The structure of the particles was studied using X-ray diffraction (XRD), while the hydrodynamic radii, particle size distributions and polydispersity of the nanoparticles were characterized using dynamic light scattering (DLS). Carbodiimide reduction was also used to functionalize the BMNPs with a molecular recognition unit (luteinizing hormone releasing hormone, LHRH) that attaches specifically to receptors that are over-expressed on the surfaces of most breast cancer cell types. The resulting nanoparticles were examined using Fourier Transform Infrared (FTIR) spectroscopy and quantitative image analysis. The implications of the results are then discussed for the potential development of magnetic nanoparticles for the specific targeting and treatment of breast cancer. - Highlights: • Biosynthesis of MNPs with clinically relevant sizes between 10 and 60 nm. • New insights into the effects of pH and processing time on nanoparticle shapes and sizes. • Successful conjugation of biosynthesized magnetite nanoparticles to LHRH ligands. • Conjugated BMNPs that are monodispersed with potential biomedical relevance. • Magnetic properties of biosynthesized MNPs suggest potential for MRI enhancement.

  17. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  18. Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.

    Science.gov (United States)

    Papadia, A; Schally, A V; Halmos, G; Varga, J L; Seitz, S; Buchholz, S; Rick, F; Zarandi, M; Bellyei, S; Treszl, A; Szalontay, L; Lucci, J A

    2011-10-01

    Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 μM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Degarelix monotherapy compared with luteinizing hormone-releasing hormone (LHRH) agonists plus anti-androgen flare protection in advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Damber, Jan Erik; Malmberg, Anders

    2016-01-01

    OBJECTIVES: The objective of this study was to assess differences in efficacy outcomes between luteinizing hormone-releasing hormone (LHRH) agonist plus antiandrogen (AA) flare protection and monotherapy with the gonadotrophin-releasing hormone antagonist degarelix in patients with prostate cancer...

  20. Plasma corticotropin releasing hormone during the feeling of induced emotions.

    Science.gov (United States)

    Martin Martins, Joao; Vale, Sónia do; Ferreira, Florbela; Fagundes, Maria Joao; Carmo, Isabel do; Saldanha, Carlota; Martins E Silva, J

    2010-01-01

    Central neuropeptides modulate behaviour. Plasma levels of neuropeptides may reflect central levels due to specific brain-to-blood transport systems. We purposed to show the modulation of plasma corticotropin releasing hormone (CRH) levels in relation to induced emotions. Three groups were defined. For experimental groups A and B, an emotionally significant movie fragment was projected for 20 min, while no film projection occurred in group C. Peripheral venous blood samples were collected before, 10 and 60 min after the film or at 0 and 30 min for group C. Total CRH was measured in plasma. Personality was evaluated by the Minnesota Multiphasic Personality Inventory (MMPI). Plasma CRH levels did not change in the condition with no movie projection - group C - 346 + or - 198 vs. 327 + or - 143 pg/mL. Plasma CRH levels dramatically increased with the projection of a dramatic movie - group A - 394 + or - 147 vs. 791 + or - 636 vs. 803 + or - 771 pg/mL, p<0.05. Plasma CRH increased less markedly in the condition with the projection of a comic movie - group B - 364 + or - 138 vs. 486 + or - 260 vs. 483 + or - 228 pg/mL, p<0.05 for differences between samples 1 and 3. Baseline plasma CRH was significantly and independently related to the neurotic triad and psychotic dyad - partial r=0.328 and 0.267, respectively, p<0.05. We conclude that plasma CRH levels increase with experimental emotion induction and that baseline levels are significantly related to behavioural traits. Plasma levels of neuropeptides may reflect central levels and may be useful in clinical medicine and in the study of behavioural disorders.

  1. Novel activity of human angiotensin I converting enzyme: release of the NH2- and COOH-terminal tripeptides from the luteinizing hormone-releasing hormone.

    OpenAIRE

    Skidgel, R A; Erdös, E G

    1985-01-01

    Angiotensin I converting enzyme (ACE; kininase II; peptidyldipeptide hydrolase, EC 3.4.15.1) cleaves COOH-terminal dipeptides from active peptides containing a free COOH terminus. We investigated the hydrolysis of luteinizing hormone-releasing hormone (LH-RH) by homogeneous human ACE. Although this decapeptide is blocked at both the NH2 and COOH termini, it was metabolized to several peptides, which were separated by HPLC and identified by amino acid analysis. A major product was the NH2-term...

  2. Anorectic actions of prolactin-releasing peptide are mediated by corticotropin-releasing hormone receptors.

    Science.gov (United States)

    Lawrence, Catherine B; Liu, Yong-Ling; Stock, Michael J; Luckman, Simon M

    2004-01-01

    Prolactin-releasing peptide (PrRP) reduces food intake and body weight and modifies body temperature when administered centrally in rats, suggesting a role in energy homeostasis. However, the mediators of PrRP's actions are unknown. The present study, therefore, first examined the possible involvement of the anorectic neuropeptides corticotropin-releasing hormone (CRH) and the melanocortins (e.g., alpha-melanocyte-stimulating hormone) in PrRP's effects on food intake and core body temperature and, second, determined if PrRP affects energy expenditure by measuring oxygen consumption (Vo2). Intracerebroventricular injection of PrRP (4 nmol) to 24-h-fasted male Sprague-Dawley rats decreased food intake and modified body temperature. Blockade of central CRH receptors by intracerebroventricular coadministration of the CRH receptor antagonist astressin (20 microg) reversed the PrRP-induced reduction in feeding. However, astressin's effect on PrRP-induced changes in body temperature was complicated because the antagonist itself caused a slight rise in body temperature. In contrast, intracerebroventricular coadministration of the melanocortin receptor-3/4 antagonist SHU-9119 (0.1 nmol) had no effect on any of PrRP's actions. Finally, intracerebroventricular injection of PrRP (4 nmol) caused a significantly greater Vo2 over a 3-h test period compared with vehicle-treated rats. These results show that the anorectic actions of PrRP are mediated by central CRH receptors but not by melanocortin receptors-3/4 and that PrRP can modify Vo2.

  3. Regulation of the hypothalamic release of thyrotropin-releasing hormone (TRH)

    NARCIS (Netherlands)

    J.M.M. Rondeel (Jan)

    1990-01-01

    textabstractThe tripeptide TRH has diverse endocrine and non-endocrine functions and is ubiquitously located in the body. Its endocrine functions relate to its role as a hypothalamic factor which stimulates the release of TSH and PRL from the adenohypophysial thyrotroph and lactotroph,

  4. Gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor are expressed at tubal ectopic pregnancy implantation sites.

    Science.gov (United States)

    Peng, Bo; Klausen, Christian; Campbell, Lisa; Leung, Peter C K; Horne, Andrew W; Bedaiwy, Mohamed A

    2016-06-01

    To investigate whether gonadotropin-releasing hormone (GnRH) and GnRH receptor (GnRHR) are expressed at tubal ectopic pregnancy sites, and to study the potential role of GnRH signaling in regulating immortalized human trophoblast cell viability. Immunohistochemical and experimental studies. Academic research laboratory. Fallopian tube implantation sites (n = 25) were collected from women with ectopic pregnancy. First-trimester human placenta biopsies (n = 5) were obtained from elective terminations of pregnancy. None. GnRH and GnRHR expression was examined by means of immunohistochemistry and histoscoring. Trophoblastic BeWo choriocarcinoma and immortalized extravillous trophoblast (HTR-8/SVneo) cell viability was examined by means of cell counting after incubation with GnRH and/or GnRH antagonist (Antide). GnRH and GnRHR immunoreactivity was detected in cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast in all women with tubal pregnancy. GnRH immunoreactivity was higher and GnRHR immunoreactivity lower in syncytiotrophoblast compared with cytotrophoblast. GnRH and GnRHR immunoreactivity was detected in adjacent fallopian tube epithelium. Whereas neither GnRH nor Antide altered HTR-8/SVneo cell viability, treatment with GnRH significantly increased the overall cell viability of BeWo cells at 48 and 72 hours, and these effects were abolished by pretreatment with Antide. GnRH and GnRHR are expressed in trophoblast cell populations and fallopian tube epithelium at tubal ectopic pregnancy sites. GnRH increases BeWo cell viability, an effect mediated by the GnRHR. Further work is required to investigate the potential role of GnRH signaling in ectopic pregnancy. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Gonadotropin‐Releasing Hormone Agonist Cotreatment During Chemotherapy May Increase Pregnancy Rate in Survivors

    National Research Council Canada - National Science Library

    Blumenfeld, Zeev; Zur, Hilli; Dann, Eldad J

    2015-01-01

    Patients who received gonadotropin‐releasing hormone agonist (GnRHa) with chemotherapy were compared with patients who were treated with chemotherapy alone to determine whether GnRHa can increase the pregnancy rate in survivors...

  6. Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms

    NARCIS (Netherlands)

    Iliadis, Stavros I; Sylvén, Sara; Hellgren, Charlotte; Olivier, Jocelien D.; Schijven, Dick; Comasco, Erika; Chrousos, George P; Sundström Poromaa, Inger; Skalkidou, Alkistis

    2016-01-01

    BACKGROUND: Peripartum depression is a common cause of pregnancy- and postpartum-related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The

  7. A 66-kDa protein of bovine hypophyseal Pars tuberalis induces luteinizing hormone release from rat Pars distalis.

    Science.gov (United States)

    Lafarque, Martha; Oliveros, Liliana

    2008-12-01

    In this study, evidence for a factor secreted by bovine hypophyseal pars tuberalis that stimulates luteinizing hormone (LH) release from rat pars distalis cells is shown. The secretion products of bovine pars tuberalis cells into the culture medium were assayed on dispersed rat pars distalis cells in 30 min incubations and superfusion experiments. The culture medium from pars tuberalis total cell populations, added at a dose of 6 microg per tube, induced the greater LH release from pars distalis cells, without effect on follicle stimulating hormone (FSH) release. After pars tuberalis cells separation on a discontinuos Percoll gradient, only the culture medium of cells from 50 and 60% strength Percoll were able to release LH from rat pars distalis cells. Therefore, cell fractions from 50 and 60% strenght Percoll were cultured together. To elicit maximal LH release (6 times the basal output), with the addition of 2 microg of pars tuberalis protein was required, suggesting that these cells produce the factor or factors which affect pars distalis gonadotrope cells. After applying the pars tuberalis culture medium on 12% SDS-PAGE, the band with biological activity was that of 66-kDal. Fifty ng protein of its eluate released almost 9 times the basal output of LH from pars distalis cells. Results suggest a modulating effect of a protein from the bovine pars tuberalis on rat cultured gonadotrope cells from the pars distalis.

  8. Predictive Value of Dental Maturity for a Positive Gonadotropin-Releasing Hormone Stimulation Test Result in Girls with Precocious Puberty.

    Science.gov (United States)

    Baik, Jee Seon; Choi, Jin Woo; Kim, Su Jin; Kim, Ji Hyun; Kim, Sollip; Kim, Jae Hyun

    2017-02-01

    Dental maturity is associated with skeletal maturity, which is advanced in girls with central precocious puberty (CPP). We investigated the performance of dental maturity as a screening method for CPP using mandibular second premolar and molar calcification stages, assessed the associated anthropometric and laboratory factors, and evaluated pubertal response predictors using the gonadotropin-releasing hormone stimulation test (GnRHST) in prepubertal and pubertal girls. A prospective case-control study was conducted in girls, aged 7.0-8.9 years, classified into pubertal (peak luteinizing hormone [LH] after GnRHST ≥ 5 IU/L), prepubertal (peak LH puberty might help determine the performance of GnRHSTs.

  9. A role for central nervous growth hormone-releasing hormone signaling in the consolidation of declarative memories.

    Directory of Open Access Journals (Sweden)

    Manfred Hallschmid

    Full Text Available Contributions of somatotropic hormonal activity to memory functions in humans, which are suggested by clinical observations, have not been systematically examined. With previous experiments precluding a direct effect of systemic growth hormone (GH on acute memory formation, we assessed the role of central nervous somatotropic signaling in declarative memory consolidation. We examined the effect of intranasally administered growth hormone releasing-hormone (GHRH; 600 µg that has direct access to the brain and suppresses endogenous GHRH via an ultra-short negative feedback loop. Twelve healthy young men learned word-pair associates at 2030 h and were administered GHRH and placebo, respectively, at 2100 h. Retrieval was tested after 11 hours of wakefulness. Compared to placebo, intranasal GHRH blunted GH release within 3 hours after substance administration and reduced the number of correctly recalled word-pairs by ∼12% (both P<0.05. The impairment of declarative memory consolidation was directly correlated to diminished GH concentrations (P<0.05. Procedural memory consolidation as examined by the parallel assessment of finger sequence tapping performance was not affected by GHRH administration. Our findings indicate that intranasal GHRH, by counteracting endogenous GHRH release, impairs hippocampal memory processing. They provide first evidence for a critical contribution of central nervous somatotropic activity to hippocampus-dependent memory consolidation.

  10. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

    Directory of Open Access Journals (Sweden)

    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  11. Growth Hormone Response after Administration of L-dopa, Clonidine, and Growth Hormone Releasing Hormone in Children with Down Syndrome.

    Science.gov (United States)

    Pueschel, Seigfried M.

    1993-01-01

    This study of eight growth-retarded children with Down's syndrome (aged 1 to 6.5 years) found that administration of growth hormone was more effective than either L-dopa or clonidine. Results suggest that children with Down's syndrome have both anatomical and biochemical hypothalamic derangements resulting in decreased growth hormone secretion and…

  12. Processing of growth hormone by rat adipocytes in primary culture: differentiation between release of intact hormone and degradative processing.

    Science.gov (United States)

    Roupas, P; Herington, A C

    1987-10-01

    Rat adipocytes in primary culture have been used to study the intracellular processing of GH. These classic target cells for GH have been shown to process GH through two pathways: a nondegradative pathway which resulted in the rapid release of intact GH, and a slower, degradative pathway which involved the degradation of GH and release of degraded ligand. Differentiation between the two pathways was on the basis of differences in their kinetics and temperature dependence. The present study has investigated the relative characteristics of the two pathways further. Incubation of [125I]human GH ([125I]hGH)-preloaded adipocytes with extracellular unlabeled hGH (400 ng/ml) resulted in an increase in the absolute amount of [125I]hGH released. The increased amount of [125I]hGH released was all intact. Extracellular, unlabeled hGH had no effect on the rate or amount of degraded [125I]hGH released. This suggests that the nondegradative pathway is sensitive to the number of internalized hormone-receptor complexes and that GH which is not immediately degraded or stored in the degradative pathway, is redirected and processed via the faster non-degradative pathway. Ammonium chloride (known to inhibit the lysosomal degradation of many polypeptide hormones) markedly inhibited the absolute amount of [125I]hGH released from preloaded adipocytes. This inhibition was due to an effect on the release of degraded [125I]hGH. NH4Cl had no effect on the rate or amount of intact [125I]hGH released. Finally, it was found that dinitrophenol and sodium fluoride (agents known to deplete cellular energy) inhibited the release of degraded GH but not intact GH suggesting that the degradative pathway involves an energy-dependent step, most likely the fusion of hormone-containing vesicles with the lysosomal membrane. The mechanism of release of intact hormone by energy-independent means is not yet known. These data indicate that the processing of GH by cultured rat adipocytes is complex and involves

  13. Consensus statement on the use of gonadotropin-releasing hormone analogs in children.

    Science.gov (United States)

    Carel, Jean-Claude; Eugster, Erica A; Rogol, Alan; Ghizzoni, Lucia; Palmert, Mark R; Antoniazzi, Franco; Berenbaum, Sheri; Bourguignon, Jean-Pierre; Chrousos, George P; Coste, Joël; Deal, Sheri; de Vries, Liat; Foster, Carol; Heger, Sabine; Holland, Jack; Jahnukainen, Kirsi; Juul, Anders; Kaplowitz, Paul; Lahlou, Najiba; Lee, Mary M; Lee, Peter; Merke, Deborah P; Neely, E Kirk; Oostdijk, Wilma; Phillip, Moshe; Rosenfield, Robert L; Shulman, Dorothy; Styne, Dennis; Tauber, Maïthé; Wit, Jan M

    2009-04-01

    Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. Preference was given to articles written in English with long-term outcome data. The US Public Health grading system was used to grade evidence and rate the strength of conclusions. When evidence was insufficient, conclusions were based on expert opinion. Participants were put into working groups with assigned topics and specific questions. Written materials were prepared and distributed before the conference, revised on the basis of input during the meeting, and presented to the full assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement. The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls <6 years old) central precocious puberty. Other key areas, such as the psychosocial effects of central precocious puberty and their alteration by gonadotropin-releasing hormone analogs, need additional study. Few controlled prospective studies have been performed with gonadotropin-releasing hormone analogs in children, and many conclusions rely in part on collective expert opinion. The conference did not endorse commonly voiced concerns regarding the use of gonadotropin-releasing hormone analogs, such as promotion of weight gain or long-term diminution of bone

  14. Endocrine archeology: do insects retain ancestrally inherited counterparts of the vertebrate releasing hormones GnRH, GHRH, TRH, and CRF?

    Science.gov (United States)

    De Loof, Arnold; Lindemans, Marleen; Liu, Feng; De Groef, Bert; Schoofs, Liliane

    2012-05-15

    Vertebrate releasing hormones include gonadotropin releasing hormone (GnRH), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRF), and thyrotropin-releasing hormone (TRH). They are synthesized in the hypothalamus and stimulate the release of pituitary hormones. Here we review the knowledge on hormone releasing systems in the protostomian lineage. We address the question: do insects have peptides that may be phylogenetically related to an ancestral GnRH, GHRH, TRH, and CRF? Such endocrine archeology has become possible thanks to the growing list of fully sequenced genomes as well as to the continuously improving bioinformatic tool set. It has recently been shown that the ecdysozoan (nematodes and arthropods) adipokinetic hormones (AKHs), the lophotrochozoan (annelids and mollusks) GnRHs as well as the protochordate GnRHs are structurally related. The adipokinetic hormone precursor-related peptides (APRPs), in locusts encoded by the same gene that contains the AKH-coding region, have been forwarded as the structural counterpart of GHRH of vertebrates. CRF is relatively well conserved in insects, in which it functions as a diuretic hormone. Members of TRH-receptor family seem to have been conserved in some arthropods, but other elements of the thyroid hormone signaling system are not. A challenging idea is that in insects the functions of the thyroid hormones were taken over by juvenile hormone (JH). Our reconstruction suggests that, perhaps, the ancestral releasing hormone precursors played a role in controlling energy metabolism and water balance, and that releasing hormone functions as present in extant vertebrates were probably secondarily acquired. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of Growth Hormone in Mice.

    Science.gov (United States)

    Xie, T Y; Ngo, S T; Veldhuis, J D; Jeffery, P L; Chopin, L K; Tschöp, M; Waters, M J; Tolle, V; Epelbaum, J; Chen, C; Steyn, F J

    2015-12-01

    Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat(-/-) mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat(-/-) mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat(-/-) mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of

  16. The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases

    Science.gov (United States)

    Daimon, Caitlin M.; Chirdon, Patrick; Maudsley, Stuart; Martin, Bronwen

    2013-01-01

    Thyrotropin releasing hormone (TRH) is primarily known as the central regulator of the hypothalamic-pituitary-thyroid (HPT) axis. However, TRH also exerts a variety of central nervous system effects independent from its activity in the HPT axis. With advancing age, decreases in TRH synthesis, expression, and activity have been demonstrated. Associated with this emerging evidence suggests that TRH is implicated in neurodegenerative diseases of aging, including Alzheimer’s disease and Parkinson’s disease. TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation. In this review, we will provide an overview of some of the roles of TRH, outside of the HPT axis, associated with pathological aging and neurodegeneration and we shall discuss the potential of TRH and TRH analogs for the treatment of neurodegenerative diseases. PMID:24199031

  17. Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

    Science.gov (United States)

    Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

    2017-10-26

    Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

  18. Follistatin, induced by thyrotropin-releasing hormone (TRH), plays no role in prolactin expression but affects gonadotropin FSHbeta expression as a paracrine factor in pituitary somatolactotroph GH3 cells.

    Science.gov (United States)

    Oride, Aki; Kanasaki, Haruhiko; Purwana, Indri N; Mutiara, Sandra; Miyazaki, Kohji

    2009-08-07

    Follistatin regulates FSHbeta gene expression by binding to and bioneutralizing activin effects. In this study, we found that thyrotropin-releasing hormone (TRH) increased follistatin gene expression in pituitary somatolactotroph GH3 cells. Treatment of GH3 with 100 nM TRH significantly increased follistatin mRNA expression as determined by real time PCR. TRH-induced follistatin expression was significantly abrogated in the presence of MEK inhibitor, U0126. Overexpression of constitutive active MEKK in GH3 cells dramatically increased follistatin expressions. Transfection of GH3 cells with follistatin siRNA reduced endogenous follistatin mRNA expression, but failed to modulate prolactin promoter activity. Prolactin mRNA levels were not affected by increasing the dose of follistatin, and TRH-induced prolactin promoter activity was not modulated in the presence of follistatin. In other experiments using pituitary gonadotroph LbetaT2 cells, activin increased FSHbeta promoter activity and mRNA expression, and follistatin completely inhibited this activin-increased FSHbeta gene expression. Treatment of GH3 cells with activin reduced the basal activity of prolactin promoter and follistatin prevented this effect. GH3 cells were co-cultured with LbetaT2 cells, which had been transfected with FSHbeta promoter-linked luciferase vectors and treated with activin in the presence of TRH. Activin-induced FSHbeta promoter activity was completely inhibited in the presence of TRH. In addition to that, FSHbeta mRNA was not detected from LbetaT2 cells which were co-cultured with GH3 cells. Our current results suggest the possibility that TRH increases follistatin gene expression in prolactin-producing cells in association with ERK pathways. Somatolactotroph-derived follistatin affects gonadotrophs by countering activin-induced FSHbeta gene expression in a paracrine fashion.

  19. Efficacy and safety of sustained-release recombinant human growth hormone in Korean adults with growth hormone deficiency.

    Science.gov (United States)

    Kim, Youngsook; Hong, Jae Won; Chung, Yoon-Sok; Kim, Sung-Woon; Cho, Yong-Wook; Kim, Jin Hwa; Kim, Byung-Joon; Lee, Eun Jig

    2014-07-01

    The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated. This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.

  20. Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma.

    Science.gov (United States)

    Szereday, Zoltan; Schally, Andrew V; Varga, Jozsef L; Kanashiro, Celia A; Hebert, Francine; Armatis, Patricia; Groot, Kate; Szepeshazi, Karoly; Halmos, Gabor; Busto, Rebeca

    2003-11-15

    Recent studies show that antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various cancers indirectly through blockage of the endocrine GH-insulin-like growth factor (IGF) I axis and directly by an action on tumor cells involving the suppression of autocrine/paracrine IGF-I, IGF-II, or GH-RH. The effectiveness of therapy with GH-RH antagonist JV-1-38 and its mechanisms of action were investigated in NCI-H838 non-small cell lung carcinoma (NSCLC) xenografted s.c. into nude mice and in vitro. Treatment with GH-RH antagonist JV-1-38 significantly (P < 0.05-0.001) inhibited tumor growth as demonstrated by a 58% decrease in final tumor volume, 54% reduction in tumor weight, and the extension of tumor-doubling time from 8.5 +/- 1.38 to 12 +/- 1.07 days as compared with controls. Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-PCR revealed the expression of mRNA for GH-RH and splice variant 1 (SV(1)) of GH-RH receptor in H838 tumors. Reverse transcription-PCR analysis also demonstrated that H838 tumors express IGF-I and IGF-I receptors. Tumoral concentration of IGF-I and its mRNA expression were significantly decreased by 25% (P = 0.05) and 65% (P < 0.001), respectively, in animals receiving JV-1-38, whereas serum IGF-I levels remained unchanged. In vitro studies showed that H838 cells secreted GH-RH and IGF-I into the medium. The growth of tumor cells in vitro was stimulated by IGF-I and inhibited by GH-RH antagonist JV-1-38 and a GH-RH antiserum. Our results extend the findings on the involvement of IGF-I in NSCLC and suggest that GH-RH may be an autocrine growth factor for H838 NSCLC. The antitumorigenic action of GH-RH antagonists could be partly direct and mediated by SV(1) of tumoral GH-RH receptors. The finding of GH-RH and SV(1) of GH-RH receptors in NSCLC provides a new approach to the treatment of this

  1. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network

    Directory of Open Access Journals (Sweden)

    Craig Alexander McArdle

    2013-11-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is the primary regulator of mammalian reproductive function in both males and females. It acts via G-protein coupled receptors on gonadotropes to stimulate synthesis and secretion of the gonadotropin hormones luteinizing hormone and follicle-stimulating hormone. These receptors couple primarily via G-proteins of the Gq/11 family, driving activation of phospholipase C and mediating GnRH effects on gonadotropin synthesis and secretion. There is also good evidence that GnRH causes activation of other heterotrimeric G-proteins (Gs and Gi with consequent effects on cyclic AMP production, as well as for effects on the soluble and particulate guanylyl cyclases that generate cGMP. Here we provide an overview of these pathways. We emphasise mechanisms underpinning pulsatile hormone signaling and the possible interplay of GnRH and autocrine or paracrine regulatory mechanisms in control of cyclic nucleotide signaling.

  2. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  3. Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone Agonist for Endometriosis: A Randomized Controlled Trial.

    Science.gov (United States)

    DiVasta, Amy D; Feldman, Henry A; Sadler Gallagher, Jenny; Stokes, Natalie A; Laufer, Marc R; Hornstein, Mark D; Gordon, Catherine M

    2015-09-01

    To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis. Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone. Hormonal add-back may mitigate these effects. Adolescents and young women (n=51) received a random, double-blind assignment to add-back with norethindrone acetate (5 mg/day) plus conjugated equine estrogens (0.625 mg/day) or norethindrone acetate plus placebo for 12 months. Body composition, bone mineral content, and bone mineral density (BMD) were obtained by dual-energy X-ray absorptiometry every 6 months. Quality-of-life measures were collected every 3 months. Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance. Thirty-four adolescents and young women completed the trial; dropouts did not differ from those who completed the trial. Bone mineral density was normal at baseline. At 12 months, total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group (bone mineral content +37 g, Padd-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy. Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content, areal BMD, and lean mass than norethindrone acetate monotherapy. ClinicalTrials.gov; www.clinicaltrials.gov, NCT00474851. I.

  4. A super-agonist of growth hormone-releasing hormone causes rapid improvement of nutritional status in patients with chronic kidney disease.

    Science.gov (United States)

    Niemczyk, Stanisław; Sikorska, Hanna; Wiecek, Andrzej; Zukowska-Szczechowska, Ewa; Załecka, Klaudia; Gorczyńska, Joanna; Kubik, Małgorzata; Czerwieńska, Beata; Gosek, Katarzyna; Veldhuis, Johannes D; Wagner, David A; Gaudreau, Pierrette; Hakonen, Tiina; Kay, Sam Wai Kit; Jouhikainen, Taneli; Schaefer, Franz

    2010-03-01

    Chronic kidney disease is frequently associated with protein-energy wasting related to chronic inflammation and a resistance to anabolic hormones such as insulin and growth hormone (GH). In this study, we determined whether a new GH-releasing hormone super-agonist (AKL-0707) improved the anabolism and nutritional status of nondialyzed patients with stage 4-5 chronic kidney disease randomized to twice daily injections of the super-agonist or placebo. After 28 days, this treatment significantly increased 24-h GH secretion by almost 400%, without altering the frequency or rhythmicity of secretory bursts or fractional pulsatile GH release, and doubled the serum insulin-like growth factor-1 level. There was a significant change in the Subjective Global Assessment from 'mildly to moderately malnourished' to 'well-nourished' in 6 of 9 patients receiving AKL-0707 but in none of 10 placebo-treated patients. By dual-energy X-ray absorptiometry, both the mean fat-free mass and the body mineral content increased, but fat mass decreased, all significantly. In the AKL-0707-treated group, both serum urea and normalized protein equivalent of nitrogen appearance significantly decreased with no change in dietary protein intake, indicating a protein anabolic effect of treatment. Thus, our study shows that stimulation of endogenous GH secretion by AKL-0707 overcomes uremic catabolism of patients with advanced chronic kidney disease.

  5. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10/sup 5//well). Cells treated with GnRH Ca/sup + +/ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca/sup + +/-free media prevented the action of GnRH. GnRH caused a rapid efflux of /sup 45/Ca/sup + +/. Both GnRH-stimulated /sup 45/Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect /sup 45/Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE/sub 2/ and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca/sup + +/ does not regulate LH release; (2) GnRH elevates intracellular Ca/sup + +/ by opening both voltage sensitive and receptor mediated Ca/sup + +/ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release.

  6. Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of U-87MG Human Glioblastoma in Nude Mice

    Directory of Open Access Journals (Sweden)

    Hippokratis Kiaris

    2000-05-01

    Full Text Available Antagonists of growth hormone-releasing hormone(GH-RH inhibit the growth of various cancers by mechanisms that involve the suppression of the insulin-like growth factor (IGF -I and/or IGF-II. In view of the importance of the IGF system in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36 were investigated in nude mice bearing subcutaneous and orthotopic xenografts of U-87MG human glioblastomas. After 4 weeks of therapy with MZ-5-156 or JV-1-36 at the dose of 20 µmg/day per animal, the final volume of subcutaneous U-87MG tumors was significantly (P < .01 decreased by 84% and 76%, respectively, as compared with controls. Treatment with GHRH antagonists also reduced tumor weight and the levels of mRNA for IGF receptor type I (IGFR-I. A reduction in the mRNA levels for IGF-II was found in tumors of mice treated with MZ-5-156. Treatment with MZ-5-156 or JV-1-36 also extended the survival of nude mice implanted orthotopically with U-87MG glioblastomas by 81% (P < .005 and 18%, respectively, as compared with the controls. Exposure in vitro to GH-RH antagonists MZ-5-156 or JV-1-36 at 1 MM concentration for 24 hours decreased the tumorigenicity of U-87MG cells in nude mice by 10% to 30% and extended the latency period for the development of subcutaneous palpable tumors by 31% to 56%, as compared with the controls. Exposure of U-87MG cells to GH-RH antagonists in vitro also resulted in a time-dependent increase in the mRNA levels of IGFR-II or a decrease in the mRNA levels of IGFR-I. mRNA for GH-RH was detected in U87MG cells and xenografts implying that GH-RH may play a role in the pathogenesis of this tumor. Our results suggest that GH-RH antagonists MZ-5-156 and JV-136 inhibit the growth of U-87MG human glioblastoma by mechanisms that involve the suppression of IGF system. Antagonistic analogs of GH-RH merit further development for the treatment of malignant glioblastoma.

  7. Changes in growth hormone-binding protein in girls with central precocious puberty treated with a depot preparation of luteinizing hormone-releasing hormone analogue.

    Science.gov (United States)

    Oliveira, S B; Donnadieu, M; Chaussain, J L

    1993-01-01

    Growth hormone-binding protein (GHBP) was studied in 11 girls with true precocious puberty, aged 7.3 +/- 0.2 years (mean +/- SE), before and after the first 6 months of treatment with luteinizing hormone-releasing hormone analogue D-Trp6-LHRH. The 125I-human GH was incubated with 150 microliters of serum, bound and free GH were separated by gel filtration. The levels of GHBP increased significantly from 24.2 +/- 1.3 to 28.1 +/- 1.9% (p pubertal spurt is mediated by a sex-steroid-induced rise in GH concentration, and they suggest that the levels of GHBP may be related to the GH secretion and its variation with treatment.

  8. Synthesis and release of luteinizing hormone in vitro: manipulations of Ca2+ environment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, T.C.; Jackson, G.L.

    1985-08-01

    The authors determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. They monitored LH synthesis when LH release was stimulated either by specific (gonadotropin-releasing hormone (GnRH)) or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of (/sup 3/H)glucosamine (glycosylation) and (/sup 14/C)alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and (/sup 14/C)alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus, glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined.

  9. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  10. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  11. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology

    NARCIS (Netherlands)

    Youssef, Mohamed A. F. M.; van der Veen, Fulco; Al-Inany, Hesham G.; Mochtar, Monique H.; Griesinger, Georg; Nagi Mohesen, Mohamed; Aboulfoutouh, Ismail; van Wely, Madelon

    2014-01-01

    Background Human chorionic gonadotropin (HCG) is routinely used for final oocyte maturation triggering in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles, but the use of HCG for this purpose may have drawbacks. Gonadotropin-releasing hormone (GnRH) agonists present an

  12. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals

    Science.gov (United States)

    Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in some mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, s...

  13. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome

    NARCIS (Netherlands)

    Bayram, N.; van Wely, M.; van der Veen, F.

    2004-01-01

    BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in

  14. Effect of gonadotropin-releasing hormone (GnRH) treatment on ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of gonadotropin-releasing hormone (GnRH) administration on the induction of multiple births in synchronized Afshari ewes. 16 cycling, multiparous fat-tailed Iranian Afshari ewes, weighing 66.5 ± 2.5 kg, were used in the trail. Estrus was synchronized using controlled ...

  15. Consensus statement on the use of gonadotropin-releasing hormone analogs in children

    DEFF Research Database (Denmark)

    Carel, Jean-Claude; Eugster, Erica A; Rogol, Alan

    2009-01-01

    for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe...

  16. Excitatory effects of thyrotropin-releasing hormone (TRH) in hypoglossal motoneurons

    DEFF Research Database (Denmark)

    Rekling, J C

    1990-01-01

    The effect of thyrotropin-releasing hormone (TRH) was studied in 30 hypoglossal motoneurons from brainstem slices of guinea pigs. Bath application of TRH resulted in an increase of the spontaneous excitatory synaptic activity, depolarization of the neurons, increase of the input resistance...

  17. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles

    NARCIS (Netherlands)

    Youssef, Mohamed A. F. M.; van der Veen, Fulco; Al-Inany, Hesham G.; Griesinger, Georg; Mochtar, Monique H.; van Wely, Madelon

    2010-01-01

    Background Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is

  18. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist assisted reproductive technology cycles

    NARCIS (Netherlands)

    Youssef, Mohamed A. F. M.; van der Veen, Fulco; Al-Inany, Hesham G.; Griesinger, Georg; Mochtar, Monique H.; van Wely, Madelon

    2010-01-01

    Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is still the

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

    Indian Academy of Sciences (India)

    2013-11-05

    Nov 5, 2013 ... Maternal hormonal interventions as a risk factor for Autism. Spectrum Disorder: An epidemiological assessment from India. MADHU POORNIMA MAMIDALA. 1. , ANUPAMA POLINEDI. 1. , PTV PRAVEEN KUMAR. 2. , N RAJESH. 3. ,. OMSAI RAMESH VALLAMKONDA. 4. , VRAJESH UDANI. 5.

  20. Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

    Science.gov (United States)

    Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

    2012-03-01

    Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Active immunization of gilts against gonadotropin-releasing hormone: effects on secretion of gonadotropins, reproductive function, and responses to agonists of gonadotropin-releasing hormone.

    Science.gov (United States)

    Esbenshade, K L; Britt, J H

    1985-10-01

    Sexually mature gilts were actively immunized against gonadotropin-releasing hormone (GnRH) by conjugating GnRH to bovine serum albumin, emulsifying the conjugate in Freund's adjuvant, and giving the emulsion as a primary immunization at Week 0 and as booster immunizations at Weeks 10 and 14. Antibody titers were evident by 2 wk after primary immunization and increased markedly in response to booster immunizations. Active immunization against GnRH caused gonadotropins to decline to nondetectable levels, gonadal steroids to decline to basal levels, and the gilts to become acyclic. Prolactin concentrations in peripheral circulation were unaffected by immunization against GnRH. The endocrine status of the hypothalamic-pituitary-ovarian axis was examined by giving GnRH and two agonists to GnRH and by ovariectomy. An i.v. injection of 100 micrograms GnRH caused release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in control animals, but not in gilts immunized against GnRH. In contrast, administration of 5 micrograms D-(Ala6, des-Gly-NH2(10] ethylamide or 5 micrograms D-(Ser-t-But6, des-Gly-NH2(10] ethylamide resulted in immediate release of LH and FSH in both control and GnRH-immunized gilts. Circulating concentrations of LH and FSH increased after ovariectomy in the controls, but remained at nondetectable levels in gilts immunized against GnRH. Prolactin concentrations did not change in response to ovariectomy. We conclude that cyclic gilts can be actively immunized against GnRH and that this causes cessation of estrous cycles and inhibits secretion of LH, FSH, and gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Signalling, cycling and desensitisation of gonadotrophin-releasing hormone receptors.

    Science.gov (United States)

    McArdle, Craig A; Franklin, J; Green, L; Hislop, J N

    2002-04-01

    down-regulation of inositol (1,4,5) trisphosphate receptors and desensitisation of Ca(2+) mobilisation in pituitary cells. The atypical resistance of the GnRH-R to desensitisation may underlie its atypical efficiency at provoking this downstream adaptive response. GnRH-Rs are also expressed in several extrapituitary sites, and these may mediate direct inhibition of proliferation of hormone-dependent cancer cells. Infection with type I GnRH-R-expressing adenovirus facilitated expression of high-affinity, PLC-coupled GnRH-R in mammary and prostate cancer cells, and these mediated pronounced antiproliferative effects of receptor agonists. No such effect was seen in cells transfected with a type II GnRH-R, implying that it is mediated most efficiently by a non-desensitising receptor. Thus it appears that the mammalian GnRH-Rs have undergone a period of rapidly accelerated molecular evolution that is of functional relevance to GnRH-Rs in pituitary and extrapituitary sites.

  3. 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 kini...

  4. Relationship between body mass index and serum testosterone concentration in patients receiving luteinizing hormone-releasing hormone agonist therapy for prostate cancer

    NARCIS (Netherlands)

    van der Sluis, Tim M.; van Moorselaar, R. Jeroen A.; Meuleman, Eric J. H.; ter Haar, Ronald W.; Bui, Hong N.; Heijboer, Annemieke C.; Vis, André N.

    2013-01-01

    To evaluate the relationship between the body mass index (BMI) and serum testosterone concentrations in men receiving luteinizing hormone-releasing hormone (LHRH) agonist therapy for prostate cancer. A total of 66 white men were included in the present study. All subjects had received LHRH agonist

  5. Corticotropin-releasing hormone neurons in the paraventricular nucleus of the human hypothalamus in subjects with normal and abnormal sex hormone status

    NARCIS (Netherlands)

    Bao, A.-M.; Swaab, D.F.

    2007-01-01

    In order to determine the role of peripheral sex hormone levels in the expression of corticotropin-releasing hormone (CRH) neurons, we investigated by means of immunocytochemistry the number of CRH neurons in the hypothalamic paraventricular nucleus (PVN) in postmortem material of young and old

  6. GATA2 mediates thyrotropin-releasing hormone-induced transcriptional activation of the thyrotropin β gene.

    Directory of Open Access Journals (Sweden)

    Kenji Ohba

    Full Text Available Thyrotropin-releasing hormone (TRH activates not only the secretion of thyrotropin (TSH but also the transcription of TSHβ and α-glycoprotein (αGSU subunit genes. TSHβ expression is maintained by two transcription factors, Pit1 and GATA2, and is negatively regulated by thyroid hormone (T3. Our prior studies suggest that the main activator of the TSHβ gene is GATA2, not Pit1 or unliganded T3 receptor (TR. In previous studies on the mechanism of TRH-induced activation of the TSHβ gene, the involvements of Pit1 and TR have been investigated, but the role of GATA2 has not been clarified. Using kidney-derived CV1 cells and pituitary-derived GH3 and TαT1 cells, we demonstrate here that TRH signaling enhances GATA2-dependent activation of the TSHβ promoter and that TRH-induced activity is abolished by amino acid substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHβ gene. In CV1 cells transfected with TRH receptor expression plasmid, GATA2-dependent transactivation of αGSU and endothelin-1 promoters was enhanced by TRH. In the gel shift assay, TRH signal potentiated the DNA-binding capacity of GATA2. While inhibition by T3 is dominant over TRH-induced activation, unliganded TR or the putative negative T3-responsive element are not required for TRH-induced stimulation. Studies using GH3 cells showed that TRH-induced activity of the TSHβ promoter depends on protein kinase C but not the mitogen-activated protein kinase, suggesting that the signaling pathway is different from that in the prolactin gene. These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHβ expression.

  7. GATA2 Mediates Thyrotropin-Releasing Hormone-Induced Transcriptional Activation of the Thyrotropin β Gene

    Science.gov (United States)

    Ohba, Kenji; Sasaki, Shigekazu; Matsushita, Akio; Iwaki, Hiroyuki; Matsunaga, Hideyuki; Suzuki, Shingo; Ishizuka, Keiko; Misawa, Hiroko; Oki, Yutaka; Nakamura, Hirotoshi

    2011-01-01

    Thyrotropin-releasing hormone (TRH) activates not only the secretion of thyrotropin (TSH) but also the transcription of TSHβ and α-glycoprotein (αGSU) subunit genes. TSHβ expression is maintained by two transcription factors, Pit1 and GATA2, and is negatively regulated by thyroid hormone (T3). Our prior studies suggest that the main activator of the TSHβ gene is GATA2, not Pit1 or unliganded T3 receptor (TR). In previous studies on the mechanism of TRH-induced activation of the TSHβ gene, the involvements of Pit1 and TR have been investigated, but the role of GATA2 has not been clarified. Using kidney-derived CV1 cells and pituitary-derived GH3 and TαT1 cells, we demonstrate here that TRH signaling enhances GATA2-dependent activation of the TSHβ promoter and that TRH-induced activity is abolished by amino acid substitution in the GATA2-Zn finger domain or mutation of GATA-responsive element in the TSHβ gene. In CV1 cells transfected with TRH receptor expression plasmid, GATA2-dependent transactivation of αGSU and endothelin-1 promoters was enhanced by TRH. In the gel shift assay, TRH signal potentiated the DNA-binding capacity of GATA2. While inhibition by T3 is dominant over TRH-induced activation, unliganded TR or the putative negative T3-responsive element are not required for TRH-induced stimulation. Studies using GH3 cells showed that TRH-induced activity of the TSHβ promoter depends on protein kinase C but not the mitogen-activated protein kinase, suggesting that the signaling pathway is different from that in the prolactin gene. These results indicate that GATA2 is the principal mediator of the TRH signaling pathway in TSHβ expression. PMID:21533184

  8. Clinical application of gonadotropin-releasing hormone analogs in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ho-Seong Kim

    2010-03-01

    Full Text Available Although the increasing incidence of central precocious puberty (CPP in Korea has recently raised public concerns about health and growth problems, there are many areas of uncertainty regarding the pathogenesis, diagnosis, and management of CPP. In this paper, we review the definition of precocity, the assessment of CPP, and the hormonal abnormalities that support the diagnosis. In addition, we review the practical guidelines regarding the clinical use of gonadotropin-releasing hormone analogs in children with CPP. Indications for treatment, determination of dosage, monitoring during treatment, and discontinuation of therapy are discussed.

  9. Changes of growth hormone-releasing hormone and somatostatin neurons in the rat hypothalamus induced by genistein: a stereological study.

    Science.gov (United States)

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Nestorović, Nataša; Medigović, Ivana; Živanović, Jasmina; Milošević, Verica

    2016-12-01

    Genistein is a plant-derived estrogenic isoflavone commonly found in dietary and therapeutic supplements, due to its potential health benefits. Growth hormone-releasing hormone (GHRH) and somatostatin (SS) are neurosecretory peptides synthesized in neurons of the hypothalamus and regulate the growth hormone secretion. Early reports indicate that estrogens have highly involved in the regulation of GHRH and SS secretions. Since little is known about the potential effects of genistein on GHRH and SS neurons, we exposed rats to genistein. Genistein were administered to adult rats in dose of 30 mg/kg, for 3 weeks. The estradiol-dipropionate treatment was used as the adequate controls to genistein. Using applied stereology on histological sections of hypothalamus, we obtained the quantitative information on arcuate (Arc) and periventricular (Pe) nucleus volume and volume density of GHRH neurons and SS neurons. Image analyses were used to obtain GHRH and SS contents in the median eminence (ME). Administration of estradiol-dipropionate caused the increase of Arc and Pe nucleus volume, SS neuron volume density, GHRH and SS staining intensity in the ME, when compared with control. Genistein treatment increased: Arc nucleus volume and the volume density of GHRH neurons (by 26%) and SS neurons (1.5 fold), accompanied by higher GHRH and SS staining intensity in the ME, when compared to the orhidectomized group. These results suggest that genistein has a significant effect on hypothalamic region, involved in the regulation of somatotropic system function, and could contribute to the understanding of genistein as substance that alter the hormonal balance.

  10. Expression and actions of corticotropin-releasing factor/diuretic hormone-like peptide (CDLP) and teneurin C-terminal associated peptide (TCAP) in the vase tunicate, Ciona intestinalis: Antagonism of the feeding response.

    Science.gov (United States)

    D'Aquila, Andrea L; Hsieh, Alan Hwa-Ruey; Hsieh, Adam Hwa-Ming; De Almeida, Reuben; Lovejoy, Sabine R; Lovejoy, David A

    2017-05-15

    Teneurin C-terminal associated peptide (TCAP) is a neuropeptide that bears some structural similarity to the corticotropin-releasing factor (CRF) family of peptides. TCAP and CRF are both implicated in the regulation of stress-related behaviors, as established in rodent models. However, in vertebrates, both TCAP and CRF possess three additional paralogous forms making vertebrate models difficult to assess with respect to TCAP-CRF interaction. As a urochordate, this species possesses single homologs of TCAP and of a CRF/Diuretic-like peptide (CDLP) in the genome, thereby establishing Ciona intestinalis as an excellent model organism to examine the interaction of these peptide systems. However, the lack of C. intestinalis synthetic peptides and specific antisera has complicated experimentation. We, therefore, prepared synthetic versions of CDLP and TCAP to prepare specific antisera and to investigate their bioactivity in this species. To analyze stress-related behaviors, a novel behavioral assay was used to characterize different types of contraction-based behaviors, using buccal opening contractions, cloacal opening contractions, lateral contractions, longitudinal contractions and expulsions. Protein and mRNA expression data indicate that the mature versions of both peptides are present in a number of tissues. With respect to behavioral activity, both TCAP- and CDLP-treated animals had distinct contraction profiles under ambient conditions. Moreover, food stimulation tests revealed that whereas CDLP-treated animals displayed a strong expulsion behavior in response to feeding, TCAP-treated animals did not show this effect. These actions are consistent with previous studies done in vertebrates. Copyright © 2016. Published by Elsevier Inc.

  11. Growth hormone (GH) and GH-releasing hormone (GHRH): Co-localization and action in the chicken testis.

    Science.gov (United States)

    Martínez-Moreno, Carlos G; López-Marín, Luz M; Carranza, Martha; Giterman, Daniel; Harvey, Steve; Arámburo, Carlos; Luna, Maricela

    2014-04-01

    Growth hormone (GH) gene expression is not confined to the pituitary gland and occurs in many extrapituitary tissues, including the chicken testis. The regulation and function of GH in extrapituitary tissues is, however, largely unknown. The possibility that chicken testicular GH might be regulated by GH-releasing hormone (GHRH), as in the avian pituitary gland, was investigated in the present study. GHRH co-localized with GH in the germinal epithelium and in interstitial zones within the chicken testes, particularly in the spermatogonia and spermatocytes. In testicular cell cultures, exogenous human GHRH1-44 induced (at 1, 10 and 100nM) a dose-related increase in GH release. Western blot analysis showed a heterogeneous pattern in the GH moieties released during GHRH stimulation. 26kDa monomer GH was the most abundant moiety under basal conditions, but 15 and 17kDa isoforms were more abundant after GHRH stimulation. GHRH treatment also increased the abundance of PCNA (proliferating cell nuclear antigen) immunoreactivity in the testes. This may have been GH-mediated, since exogenous GH similarly increased the incorporation of ((3)H)-thymidine into cultured testicular cells and increased their metabolic activity, as determined by increased MTT reduction. Furthermore, GH and GHRH immunoneutralization blocked GHRH-stimulated proliferative activity. In summary, these results indicate that GHRH stimulates testicular GH secretion in an autocrine or paracrine manner. Data also demonstrate proliferative actions of GHRH on testicular cell number and suggest that this action is mediated by local GH production. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Characteristics of prolactin-releasing response to salsolinol (SAL) and thyrotropin-releasing hormone (TRH) in ruminants.

    Science.gov (United States)

    Hashizume, T; Onodera, Y; Shida, R; Isobe, E; Suzuki, S; Sawai, K; Kasuya, E; Nagy, G M

    2009-02-01

    The secretion of prolactin (PRL) is stimulated by thyrotropin-releasing hormone (TRH), and inhibited by dopamine (DA). However, we have recently demonstrated that salsolinol (SAL), a DA-derived endogenous compound, is able to stimulate the release of PRL in ruminants. The aims of the present study were to compare the characteristics of the PRL-releasing response to SAL and TRH, and examine the relation between the effects that SAL and DA exert on the secretion of PRL in ruminants in vivo and in vitro. Three consecutive intravenous (i.v.) injections of SAL (5mg/kg body weight (b.w.): 19.2micromol/kgb.w.) or TRH (1microg/kgb.w.: 2.8nmol/kgb.w.) at 2-h intervals increased plasma PRL levels after each injection in goats (PTRH. There were no significant differences in each peak value between the groups. The rate of decrease in PRL levels following the peak was attenuated in SAL-treated compare to TRH-treated animals (PTRH (10(-8)M) significantly increased the release of PRL following both 15- and 30-min incubation periods (PTRH-induced release of PRL for a 2-h incubation period in the AP cells (PTRH. Furthermore, they also show that the secretion of PRL is under the inhibitory control of DA, and SAL does not antagonize the DA receptor's action.

  13. The psychoneuromedulator role of corticotrophin releasing hormone in women with Polycystic Ovary

    Directory of Open Access Journals (Sweden)

    Farideh zafari Zangeneh

    2016-10-01

    Full Text Available   The psychoneuromedulator role of corticotrophin releasing hormone in women with Polycystic Ovary Farideh Zafari Zangeneh1*, Mohammad Mehdi Naghizadeh2 Masoumeh Masoumi1 Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran Department of Community Medicine, Medical Faculty, Fasa University of Medical Sciences, Fasa, Iran Address: Reproductive Health Research Center, Imam Hospital Complex, Keshavarz Blvd., Tehran, Iran.     E-mail: Zangeneh14@gmail.com Tel. +982166581616 Fax No.: +982166581658 Abstract Background: Polycystic ovary syndrome (PCOS is a common complex condition in women associated with reproductive and metabolic systems and also psychological disorders. There is considerable evidence to suggest that the sympathetic nervous system is involved in PCO and metabolic syndroms. Noradrenalin (NA, corticotrophin releasing hormone (CRH and nerve growth factor (NGF are the strong stimulants for two axes: hypothalamic-pituitary-adrenal (HPA and hypothalamic-pituitary-ovarian (HPO axes which are regulators for the female reproductive system. Following previous studies on sympathetic nervous system overactivity in PCOS, the main purpose of this study is to evaluate the role of CRH and NGF as two important findings from the perspective of the psycho-emotional. Methods: This case/control study has been down in Reproductive Health Research Center of Imam Khomeini Hospital, Tehran, Iran in 2015. 170 women participated in this study with 20-40 years of age and body mass index (BMI of less than 28. Data analysis was using by t-tests, Chi-square and Mann Whitney.   Results: Serum levels CRH and NGF in patients with polycystic ovary was significantly lower than the control group (p<0.001. This reduction can disrupt two neural axes and the sympathetic nervous system activity and  have a  fundamental role in psycho-emotional reactions in women with PCOS. Moreover, using demographic questionnaire quantitative and

  14. Premenstrual Exacerbation of Life-Threatening Asthma: Effect of Gonadotrophin Releasing Hormone Analogue Therapy

    Directory of Open Access Journals (Sweden)

    Alun L Edwards

    1996-01-01

    Full Text Available Variability in the severity of asthma during various phases of the menstrual cycle has been frequently suspected. However, the hormonal changes that might affect mediators of bronchospasm have yet to be elucidated. The case of a 41-year-old woman suffering from longstanding asthma with life-threatening exacerbations is reported. The patient was treated with buserelin, a gonadotropin releasing hormone (GnRH analogue, which created a temporary chemical menopause and thus permitted diagnosis of a premenstrual exacerbation of asthma and offered insight into potential therapy. GnRH analogues may therefore be of value in assessing women with severe asthma suspected to vary with the menstrual cycle. The addition of estrogens and progestins at the same time as treatment with GnRH analogue may be of value in determining the role of these hormones in the pathogenesis of menstrually related exacerbations of asthma.

  15. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E

    Science.gov (United States)

    Karavolos, Michail H; Bulmer, David M; Spencer, Hannah; Rampioni, Giordano; Schmalen, Ira; Baker, Stephen; Pickard, Derek; Gray, Joe; Fookes, Maria; Winzer, Klaus; Ivens, Alasdair; Dougan, Gordon; Williams, Paul; Khan, C M Anjam

    2011-01-01

    Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling. PMID:21331094

  16. Effect of gonadotropin-releasing hormone agonist on a uterine arteriovenous malformation.

    Science.gov (United States)

    Morikawa, Mamoru; Yamada, Takashi; Yamada, Hideto; Minakami, Hisanori

    2006-09-01

    The effect of gonadotropin-releasing hormone agonist (GnRHa) on uterine arteriovenous malformations (AVM) is not well known. A 37-year-old woman with a previous cesarean was diagnosed as having a uterine AVM after a spontaneous abortion with massive vaginal bleeding. The AVM decreased in size from 5.1 x 3.8 cm to 1.4 x 1.0 cm after 6 months of therapy with a GnRHa. Uterine artery embolization conducted after the GnRH therapy resulted in complete disappearance of the AVM. The patient's menstrual cycles and ovulation resumed 3 months after uterine artery embolization. Gonadotropin-releasing hormone agonist therapy reduced the size of the uterine AVM. Thus, GnRHa therapy may be useful for uterine AVM in situations where uterine artery embolization must be postponed.

  17. Aggressive angiomyxoma of the vulva: dramatic response to gonadotropin-releasing hormone agonist therapy

    Directory of Open Access Journals (Sweden)

    Azar Danesh

    2007-08-01

    Full Text Available

    Aggressive angiomyxoma is a rare soft tissue neoplasm that usually arises within the perineum. It often occurs as a vulvar mass and clinically simulates a Bartholin's gland cyst. Most patients are in the second or third decade of life, but some cases have also been reported in children. This is the report of a 21 year old woman with 4.5 × 3 × 1.5 cm mass in right labia major. The patient underwent wide local excision surgical treatment. Histological examination showed high vascular myxoid tumor containing spindle cells. Immunohistochemical study of cells showed positive reaction to estrogen and progesterone and negative reaction to S100, SMA and desmin. Treatment with a gonadotropin-releasing hormone agonist was administered to deal with residual tumor and prevent local recurrence for 6 months.
    KEY WORDS: Aggressive angiomyxoma, vulva, pregnancy, Gonadotropin releasing hormone agonist.

  18. 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

  19. Melatonin improves memory acquisition under stress independent of stress hormone release.

    Science.gov (United States)

    Rimmele, Ulrike; Spillmann, Maria; Bärtschi, Carmen; Wolf, Oliver T; Weber, Cora S; Ehlert, Ulrike; Wirtz, Petra H

    2009-03-01

    Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. Fifty healthy young men received a single oral dose of either 3 mg melatonin (n = 27) or placebo medication (n = 23). One hour later, they were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). During stress, subjects encoded objects distributed in the test room, for which memory was assessed a day later ("memory encoding under stress"). Fifteen minutes following stress, memory retrieval for words learnt the day before was tested ("memory retrieval after stress"). Plasma epinephrine and norepinephrine levels, salivary free cortisol levels and psychological responses (attention, wakefulness) were repeatedly measured before and after stress exposure. Melatonin specifically enhanced recognition memory accuracy of objects encoded under stress (p cortisol levels were highest, retrieval of memories acquired the day before was not influenced by melatonin. Moreover, melatonin did not influence stress-induced elevation of catecholamine and cortisol levels which in turn did not correlate with the effects of melatonin on memory. The findings point to a primary action of melatonin on central nervous stimulus processing under conditions of stress and possibly on memory consolidation and exclude any substantial suppressive action of the substance on hormonal stress responses.

  20. Deficiency of growth hormone-releasing hormone signaling is associated with sleep alterations in the dwarf rat.

    Science.gov (United States)

    Obál, F; Fang, J; Taishi, P; Kacsóh, B; Gardi, J; Krueger, J M

    2001-04-15

    The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.

  1. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone.

    Science.gov (United States)

    Jung, Mo Kyung; Song, Kyung Chul; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

    2014-12-01

    There is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP. We reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23). In the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm) was significantly higher than the initial PAH (156.6±3.96 cm) (Pheight SDS for BA was also increased during treatment. AH (159.3±5.33 cm) was also higher than the initial PAH (154.6±2.55 cm) (PHeight gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment. In CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

  2. Structural and functional divergence of growth hormone-releasing hormone receptors in early sarcopterygians: lungfish and Xenopus.

    Directory of Open Access Journals (Sweden)

    Janice K V Tam

    Full Text Available The evolutionary trajectories of growth hormone-releasing hormone (GHRH receptor remain enigmatic since the discovery of physiologically functional GHRH-GHRH receptor (GHRHR in non-mammalian vertebrates in 2007. Interestingly, subsequent studies have described the identification of a GHRHR(2 in chicken in addition to the GHRHR and the closely related paralogous receptor, PACAP-related peptide (PRP receptor (PRPR. In this article, we provide information, for the first time, on the GHRHR in sarcopterygian fish and amphibians by the cloning and characterization of GHRHRs from lungfish (P. dolloi and X. laevis. Sequence alignment and phylogenetic analyses demonstrated structural resemblance of lungfish GHRHR to their mammalian orthologs, while the X. laevis GHRHR showed the highest homology to GHRHR(2 in zebrafish and chicken. Functionally, lungfish GHRHR displayed high affinity towards GHRH in triggering intracellular cAMP and calcium accumulation, while X. laevis GHRHR(2 was able to react with both endogenous GHRH and PRP. Tissue distribution analyses showed that both lungfish GHRHR and X. laevis GHRHR(2 had the highest expression in brain, and interestingly, X. laevis(GHRHR2 also had high abundance in the reproductive organs. These findings, together with previous reports, suggest that early in the Sarcopterygii lineage, GHRHR and PRPR have already established diverged and specific affinities towards their cognate ligands. GHRHR(2, which has only been found in xenopus, zebrafish and chicken hitherto, accommodates both GHRH and PRP.

  3. Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure.

    Science.gov (United States)

    Gesmundo, Iacopo; Miragoli, Michele; Carullo, Pierluigi; Trovato, Letizia; Larcher, Veronica; Di Pasquale, Elisa; Brancaccio, Mara; Mazzola, Marta; Villanova, Tania; Sorge, Matteo; Taliano, Marina; Gallo, Maria Pia; Alloatti, Giuseppe; Penna, Claudia; Hare, Joshua M; Ghigo, Ezio; Schally, Andrew V; Condorelli, Gianluigi; Granata, Riccarda

    2017-11-07

    It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH 2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gα s and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy. Copyright © 2017 the Author(s). Published by PNAS.

  4. Menstruation recovery after chemotherapy and luteinizing hormone-releasing hormone agonist plus tamoxifen therapy for premenopausal patients with breast cancer.

    Science.gov (United States)

    Sakurai, Kenichi; Matsuo, Sadanori; Enomoto, Katsuhisa; Amano, Sadao; Shiono, Motomi

    2011-01-01

    Little is known about the period required for menstruation recovery after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen therapy following chemotherapy. In this study we investigated the period required for menstruation recovery after the therapy. The subjects comprised 105 premenopausal breast cancer patients who had undergone surgery. All patients were administered an LH-RH agonist for 24 months and tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the status of menstruation recovery was examined. Menstruation resumed in 16 cases (15.2%) after the last LH-RH agonist treatment session. The mean period from the last LH-RH agonist treatment to the recovery of menstruation was 6.9 months. The rate of menstruation recovery was 35.5% in patients aged 40 years or younger and 8.0% in those aged 41 years or older, and it was significantly higher in those aged 40 years or younger. The period until menstruation recovery tended to be longer in older patients at the end of treatment. This study showed that menstruation resumed after treatment at higher rates in younger patients. However, because it is highly likely that ovarian function will be destroyed by the treatment even in young patients, it is considered necessary to explain the risk to patients and obtain informed consent before introducing this treatment modality.

  5. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Science.gov (United States)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  6. Kisspeptin Stimulates Growth Hormone Release by Utilizing Neuropeptide Y Pathways and Is Dependent on the Presence of Ghrelin in the Ewe.

    Science.gov (United States)

    Foradori, Chad D; Whitlock, Brian K; Daniel, Jay A; Zimmerman, Arthur D; Jones, Melaney A; Read, Casey C; Steele, Barbara P; Smith, Jeremy T; Clarke, Iain J; Elsasser, Theodore H; Keisler, Duane H; Sartin, James L

    2017-10-01

    Although kisspeptin is the primary stimulator of gonadotropin-releasing hormone secretion and therefore the hypothalamic-pituitary-gonadal axis, recent findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Here we show that central delivery of kisspeptin causes a robust rise in plasma GH in fasted but not fed sheep. Kisspeptin-induced GH secretion was similar in animals fasted for 24 hours and those fasted for 72 hours, suggesting that the factors involved in kisspeptin-induced GH secretion are responsive to loss of food availability and not the result of severe negative energy balance. Pretreatment with the neuropeptide Y (NPY) Y1 receptor antagonist, BIBO 3304, blocked the effects of kisspeptin-induced GH release, implicating NPY as an intermediary. Kisspeptin treatment induced c-Fos in NPY and GH-releasing hormone (GHRH) cells of the arcuate nucleus. The same kisspeptin treatment resulted in a reduction in c-Fos in somatostatin (SS) cells in the periventricular nucleus. Finally, blockade of systemic ghrelin release or antagonism of the ghrelin receptor eliminated or reduced the ability of kisspeptin to induce GH release, suggesting the presence of ghrelin is required for kisspeptin-induced GH release in fasted animals. Our findings support the hypothesis that during short-term fasting, systemic ghrelin concentrations and NPY expression in the arcuate nucleus rise. This permits kisspeptin activation of NPY cells. In turn, NPY stimulates GHRH cells and inhibits SS cells, resulting in GH release. We propose a mechanism by which kisspeptin conveys reproductive and hormone status onto the somatotropic axis, resulting in alterations in GH release. Copyright © 2017 Endocrine Society.

  7. The role of kisspeptin-GPR54 signaling in the tonic regulation and surge release of gonadotropin-releasing hormone/luteinizing hormone.

    Science.gov (United States)

    Dungan, Heather M; Gottsch, Michelle L; Zeng, Hongkui; Gragerov, Alexander; Bergmann, John E; Vassilatis, Demetrios K; Clifton, Donald K; Steiner, Robert A

    2007-10-31

    The Kiss1 gene codes for kisspeptin, which binds to GPR54, a G-protein-coupled receptor. Kisspeptin and GPR54 are expressed in discrete regions of the forebrain, and they have been implicated in the neuroendocrine regulation of reproduction. Kiss1-expressing neurons are thought to regulate the secretion of gonadotropin-releasing hormone (GnRH) and thus coordinate the estrous cycle in rodents; however, the precise role of kisspeptin-GPR54 signaling in the regulation of gonadotropin secretion is unknown. In this study, we used female mice with deletions in the GPR54 gene [GPR54 knock-outs (KOs)] to test the hypothesis that kisspeptin-GPR54 signaling provides the drive necessary for tonic GnRH/luteinizing hormone (LH) release. We predicted that tonic GnRH/LH secretion would be disrupted in GPR54 KOs and that such animals would be incapable of showing a compensatory rise in LH secretion after ovariectomy. As predicted, we found that GPR54 KO mice do not exhibit a postovariectomy rise in LH, suggesting that tonic GnRH secretion is disrupted in the absence of kisspeptin-GPR54 signaling. We also postulated that kisspeptin-GPR54 signaling is critical for the generation of the estradiol (E)-induced GnRH/LH surge and thus E should be incapable of inducing an LH surge in the absence of GPR54. However, we found that E induced Fos expression in GnRH neurons and produced a GnRH-dependent LH surge in GPR54 KOs. Thus, in mice, kisspeptin-GPR54 signaling is required for the tonic stimulation of GnRH/LH secretion but is not required for generating the E-induced GnRH/LH surge.

  8. Binding properties of solubilized gonadotropin-releasing hormone receptor: role of carboxylic groups

    Energy Technology Data Exchange (ETDEWEB)

    Hazum, E.

    1987-11-03

    The interaction of /sup 125/I-buserelin, a superactive agonist of gonadotropin-releasing hormone (GnRH), with solubilized GnRH receptor was studied. The highest specific binding of /sup 125/I-buserelin to solubilized GnRH receptor is evident at 4/sup 0/C, and equilibrium is reached after 2 h of incubation. The soluble receptor retained 100% of the original binding activity when kept at 4 or 22/sup 0/C for 60 min. Mono- and divalent cations inhibited, in a concentration-dependent manner, the binding of /sup 125/I-buserelin to solubilized GnRH receptor. Monovalent cations require higher concentrations than divalent cations to inhibit the binding. Since the order of potency with the divalent cations was identical with that of their association constants to dicarboxylic compounds, it is suggested that there are at least two carboxylic groups of the receptor that participate in the binding of the hormone. The carboxyl groups of sialic acid residues are not absolutely required for GnRH binding since the binding of /sup 125/I-buserelin to solubilized GnRH receptor was only slightly affected by pretreatment with neuraminidase and wheat germ agglutinin. The finding that polylysines stimulate luteinizing hormone (LH) release from pituitary cell cultures with the same efficacy as GnRH suggest that simple charge interactions can induce LH release. According to these results, the authors propose that the driving force for the formation of the hormone-receptor complex is an ionic interaction between the positively charged amino acid arginine in position 8 and the carboxyl groups in the binding site.

  9. Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS): studies in hypopituitary and healthy subjects

    DEFF Research Database (Denmark)

    Bach, Ermina; Møller, Andreas Buch; Jørgensen, Jens Otto Lunde

    2016-01-01

    OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release...... of stress hormones. We compared the metabolic effects of LPS in hypopituitary patients (HP) (in the absence of pituitary stress hormone responses) and healthy control subjects (CTR) (with normal pituitary stress hormone responses). DESIGN: Single blind randomized. METHODS: We compared effects of LPS...

  10. Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Bastian Zimmer

    2016-06-01

    Full Text Available Human pluripotent stem cells (hPSCs provide an unlimited cell source for regenerative medicine. Hormone-producing cells are particularly suitable for cell therapy, and hypopituitarism, a defect in pituitary gland function, represents a promising therapeutic target. Previous studies have derived pituitary lineages from mouse and human ESCs using 3D organoid cultures that mimic the complex events underlying pituitary gland development in vivo. Instead of relying on unknown cellular signals, we present a simple and efficient strategy to derive human pituitary lineages from hPSCs using monolayer culture conditions suitable for cell manufacturing. We demonstrate that purified placode cells can be directed into pituitary fates using defined signals. hPSC-derived pituitary cells show basal and stimulus-induced hormone release in vitro and engraftment and hormone release in vivo after transplantation into a murine model of hypopituitarism. This work lays the foundation for future cell therapy applications in patients with hypopituitarism.

  11. Treatment of endometriosis with a delayed release preparation of the agonist D-Trp6-luteinizing hormone-releasing hormone: long-term follow-up in a series of 50 patients.

    Science.gov (United States)

    Zorn, J R; Mathieson, J; Risquez, F; Comaru-Schally, A M; Schally, A V

    1990-03-01

    Fifty patients with proven endometriosis were treated for 6 to 9 months with a delayed release preparation of microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp6-LH-RH, injected intramuscularly at monthly intervals. After a transitory ovarian stimulation at the onset of treatment, serum estradiol was suppressed to menopausal levels (50 pg/mL). This state of hypogonadism was reversible after the discontinuation of treatment, and menses resumed within 4 months after the last injection. Pelvic pain was relieved during treatment in 87.5% of patients. After a follow-up period of up to 37 months, 24 patients are in clinical remission and 9 experienced recurrence of endometriosis 7 to 14 months after completing treatment. One patient failed to respond to therapy with the agonist and 7 patients were lost to follow-up. Among 16 previously infertile patients with no other factors contributing to infertility, 7 became pregnant; 2 of these pregnancies were the result of gamete intrafallopian transfers. An eighth patient without documented infertility also conceived spontaneously. Side effects due to hypoestrogenism were reported by nearly all patients. In conclusion, D-Trp6-LH-RH microcapsules are effective and easily-administered agents for the treatment of endometriosis.

  12. The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.

    Science.gov (United States)

    Diedrich, K; Ludwig, M; Felberbaum, R E

    2001-09-01

    Gonadotropin-releasing hormone (GnRH)-antagonists can suppress the pituitary hormone secretion completely within a few hours, allowing the avoidance of premature luteinization within controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART) by midcycle administration. Two different protocols were described, which were widely used in COH in several phase II and III studies as well as in clinical practice since the GnRH-antagonists Cetrorelix (Cetrotidesound recording copyright sign; Serono International S.A., Geneva, Switzerland) and Ganirelix (Orgalutansound recording copyright sign, Antagonsound recording copyright sign; Organon, Oss, The Netherlands) are available on the market. Cetrorelix was applied in single- and multiple-dose protocols; Ganirelix was used until now only according to the multiple-dose protocol. Fertilization rates of >60% as well as clinical pregnancy rates of about 30% per transfer sound most promising. Estradiol secretion is not compromised by the GnRH-antagonists using recombinant follicle-stimulating hormone (FSH) for COH. The incidence of a premature leutinizing hormone (LH) surge is far below 2% while the pituitary response remains preserved, allowing the induction of ovulation by GnRH or GnRH-agonists. However, luteal phase support remains mandatory. The incidence of severe ovarian hyperstimulation syndrome (OHSS) seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened. Without any doubt GnRH-antagonists have the potential to become the new standard for controlled ovarian hyperstimulation.

  13. Inhibition of growth and reduction in tumorigenicity of UCI-107 ovarian cancer by antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide.

    Science.gov (United States)

    Chatzistamou, I; Schally, A V; Varga, J L; Groot, K; Armatis, P; Bajo, A M

    2001-11-01

    To evaluate the tumor inhibitory activities of antagonists of growth hormone-releasing hormone (GH-RH) and vasoactive intestinal peptide (VIP) in UCI-107 human ovarian cancer model, and to investigate the role of the insulin-like growth factor (IGF) system in the response. In the present study we investigated the effects of GH-RH antagonist JV-1-36 and VIP antagonist JV-1-52, on the growth and tumorigenicity of UCI-107 ovarian cell carcinoma xenografted into nude mice. Studies on the effects of hGH-RH(1-29)NH2, IGF-I, IGF-II, JV-1-36, and JV-1-52 on the proliferation of UCI-107 cells cultured in vitro were also performed. After 22 days of therapy with JV-1-36 or JV-1-52 at the dose of 20 microg/day, the final volume of UCI-107 tumors was significantly (PUCI-107 cells in nude mice. All ten mice injected with cells treated with medium alone developed tumors within 23 days after cell inoculation, while only eight of ten and four of ten mice injected with cells exposed to JV-1-36 or JV-1-52, respectively, had tumors. In vitro exposure of UCI-107 cells to 5-35 ng/ml IGF-II produced a significant suppression in the rate of cell proliferation (P UCI-107 ovarian cell carcinoma by mechanisms that appear to involve direct effects on the cancer cells.

  14. Effects of administration of two growth hormone-releasing hormone plasmids to gilts on sow and litter performance for the subsequent three gestations.

    Science.gov (United States)

    Brown, Patricia A; Khan, Amir S; Draghia-Akli, Ruxandra; Pope, Melissa A; Bodles-Brakhop, Angela M; Kern, Douglas R

    2012-09-01

    To determine whether a novel optimized plasmid carrying the porcine growth hormone-releasing hormone (GHRH) wild-type cDNA administered at a lower dose was as effective at eliciting physiologic responses as a commercial GHRH plasmid approved for use in Australia. 134 gilts. Estrus was synchronized and gilts were bred. Pregnant gilts were assigned to 2 treatment groups (40 gilts/group) or 1 untreated control group (24 gilts). Gilts in one of the treatment groups received the commercial GHRH plasmid, whereas gilts in the other treatment group received a novel optimized GHRH plasmid; both plasmids were administered IM in the right hind limb, which was followed by electroporation. Sow and litter performance were monitored for the 3 gestations after treatment. A significant increase in insulin-like growth factor-I concentrations, decrease in perinatal mortality rate, increase in the number of pigs born alive, and increase in the weight and number of pigs weaned were detected for both groups receiving the GHRH-expressing plasmids, compared with values for the control group. Additionally, there was a significant decrease in sow attrition in GHRH-treated females, compared with attrition in the control group, during the 3 gestations after treatment. Both of the GHRH plasmids provided significant benefits for sow performance and baby pig survivability for pregnant and lactating sows and their offspring during the 3 gestations after treatment, compared with results for untreated control gilts. Use of a novel optimized plasmid reduced the effective plasmid dose in these large mammals.

  15. [Direct and indirect costs of luteinising hormone-releasing hormone analogues in the treatment of locally advanced or metastatic prostate cancer in Italy].

    Science.gov (United States)

    Fadda, Valeria; Maratea, Dario

    2015-12-01

    When analyzing the use of luteinizing hormone-releasing hormone (LHRH) analogues for different clinical indications, current available evidence does not support a presumed drug class effect among the various LHRH in the treatment of prostate cancer. The following search key words were entered in the PubMed database and the NICE and FDA websites: “LHRH agonist AND prostatic cancer”, “androgen deprivation therapy”, “androgen suppression”, “buserelin”, “leuprorelin”, “goserelin”,“triptorelin”, “degarelix”. The direct costs included the following items: follow-up visits, diagnostic exams (e.g. prostate-specific antigen PSA) and drug costs. The indirect costs included working days lost by the patient. With intermittent therapy as a reference, leuprorelin injectable solution of 22,25 mg was associated with the lowest cost and degarelix with the highest cost. However, given the mandatory presence of a nurse for drug injection, the buserelin depot formulation was associated with the lowest cost. If the costs for hospital visits were added to drug costs, differences between the various therapeutic strategies were less remarkable. Our study showed how various factors (e.g. route of administration, frequency of administration, presence of a nurse for drug reconstitution and injection) should be taken into account by decision makers in addition to the price of drugs.

  16. Gonadotropin-releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio

    Directory of Open Access Journals (Sweden)

    Ryo eNishiguchi

    2012-10-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is an evolutionarily conserved neuropeptide with 10 amino acid residues, of which several structural variants exist. A molecular form known as GnRH2 ([His5 Trp7 Tyr8]GnRH, also known as chicken GnRH II is widely distributed in vertebrates except for rodents, and has recently been implicated in the regulation of feeding behavior in goldfish. However, the influence of GnRH2 on feeding behavior in other fish has not yet been studied. In the present study, therefore, we investigated the role of GnRH2 in the regulation of feeding behavior in a zebrafish model, and examined its involvement in food intake after intracerebroventricular (ICV administration. ICV injection of GnRH2 at 0.1 and 1 pmol/g body weight (BW induced a marked decrease of food consumption in a dose-dependent manner during 30 min after feeding. Cumulative food intake was significantly decreased by ICV injection of GnRH2 at 1 pmol/g BW during the 30-min post-treatment observation period. The anorexigenic action of GnRH2 was completely blocked by treatment with the GnRH type I receptor antagonist Antide at 50 pmol/g BW. We also examined the effect of feeding condition on the expression level of the GnRH2 transcript in the hypothalamus. Levels of GnRH2 mRNA obtained from fish that had been provided excess food for 7 days were higher than those in fish that had been fed normally. These results suggest that, in zebrafish, GnRH2 acts as an anorexigenic factor, as is the case in goldfish.

  17. Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge.

    Science.gov (United States)

    Clarkson, Jenny; d'Anglemont de Tassigny, Xavier; Moreno, Adriana Santos; Colledge, William H; Herbison, Allan E

    2008-08-27

    Kisspeptin and its receptor GPR54 have recently been identified as key signaling partners in the neural control of fertility in animal models and humans. The gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons of the neural network controlling fertility and are suspected to be the primary locus of kisspeptin-GPR54 signaling. Using mouse models, the present study addressed whether kisspeptin and GPR54 have a key role in the activation of GnRH neurons to generate the luteinizing hormone (LH) surge responsible for ovulation. Dual-label immunocytochemistry experiments showed that 40-60% of kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) expressed estrogen receptor alpha and progesterone receptors. Using an ovariectomized, gonadal steroid-replacement regimen, which reliably generates an LH surge, approximately 30% of RP3V kisspeptin neurons were found to express c-FOS in surging mice compared with 0% in nonsurging controls. A strong correlation was found between the percentage of c-FOS-positive kisspeptin neurons and the percentage of c-FOS-positive GnRH neurons. To evaluate whether kisspeptin and/or GPR54 were essential for GnRH neuron activation and the LH surge, Gpr54- and Kiss1-null mice were examined. Whereas wild-type littermates all exhibited LH surges and c-FOS in approximately 50% of their GnRH neurons, none of the mutant mice from either line showed an LH surge or any GnRH neurons with c-FOS. These observations provide the first evidence that kisspeptin-GPR54 signaling is essential for GnRH neuron activation that initiates ovulation. This broadens considerably the potential roles and therapeutic possibilities for kisspeptin and GPR54 in fertility regulation.

  18. Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

    Science.gov (United States)

    Merchenthaler, I; Lennard, D E; López, F J; Negro-Vilar, A

    1993-01-01

    The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility--i.e., gender-specific determination of LHRH neurons coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of

  19. Luteinizing Hormone Secretion during Gonadotropin-Releasing Hormone Stimulation Tests in Obese Girls with Central Precocious Puberty.

    Science.gov (United States)

    Lee, Hae Sang; Yoon, Jong Seo; Hwang, Jin Soon

    2016-12-01

    Girls with precocious puberty have high luteinizing hormone (LH) levels and advanced bone age. Obese children enter puberty at earlier ages than do non-obese children. We analyzed the effects of obesity on LH secretion during gonadotropin-releasing hormone (GnRH) tests in girls with precocious puberty. A total of 981 subjects with idiopathic precocious puberty who had undergone a GnRH stimulation testing between 2008 and 2014 were included in the study. Subjects were divided into three groups based on body mass index (BMI). Auxological data and gonadotropin levels after the GnRH stimulation test were compared. In Tanner stage 2 girls, peak stimulated LH levels on GnRH test were 11.9±7.5, 10.4±6.4, and 9.1±6.1 IU/L among normal-weight, overweight, and obese subjects, respectively (p=0.035 for all comparisons). In Tanner stage 3 girls, peak stimulated LH levels were 14.9±10.9, 12.8±7.9, and 9.6±6.0 IU/L, respectively (p=0.022 for all comparisons). However, in Tanner stage 4 girls, peak stimulated LH levels were not significantly different among normal, overweight, and obese children. On multivariate analysis, BMI standard deviation score was significantly and negatively associated with peak LH (β=-1.178, p=0.001). In girls with central precocious puberty, increased BMI was associated with slightly lower peak stimulated LH levels at early pubertal stages (Tanner stages 2 and 3). This association was not valid in Tanner stage 4 girls.

  20. Thyrotropin-releasing hormone inhibits melanin concentrating hormone neurons- implications for TRH mediated anorexic and arousal actions

    Science.gov (United States)

    Zhang, Xiaobing; van den Pol, Anthony N.

    2013-01-01

    Thyrotropin-releasing hormone (TRH) increases activity and decreases food intake, body weight, and sleep, in part through hypothalamic actions. The mechanism of this action is unknown. Melanin-concentrating hormone (MCH) and hypocretin/orexin neurons in the lateral hypothalamus (LH) together with neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the arcuate nucleus play central roles in energy homeostasis. Here, we provide electrophysiological evidence from GFP-reporter transgenic mouse brain slices that shows TRH modulates the activity of MCH neurons. Using whole-cell current-clamp recording, we unexpectedly found that TRH and its agonist, montrelin, dose-dependently inhibited MCH neurons. Consistent with previous reports, TRH excited hypocretin/orexin neurons. No effect was observed on arcuate nucleus POMC or NPY neurons. The TRH inhibition of MCH neurons was eliminated by bicuculline and tetrodotoxin, suggesting that the effect was mediated indirectly through synaptic mechanisms. TRH increased spontaneous IPSC frequency without affecting amplitude and had no effect on miniature IPSCs or EPSCs. Immunocytochemistry revealed little interaction between TRH axons and MCH neurons, but showed TRH axons terminating on or near GABA neurons. TRH inhibition of MCH neurons was attenuated by Na+-Ca2+ exchanger (NCX) inhibitors, TRPC channel blockers and the phospholipase C inhibitor U-73122. TRH excited LH GABA neurons, and this was also reduced by NCX inhibitors. Finally, TRH attenuated the excitation of MCH neurons by hypocretin. Taken together, our data suggest that TRH inhibits MCH neurons by increasing synaptic inhibition from local GABA neurons. Inhibition of MCH neurons may contribute to the TRH-mediated reduction in food intake and sleep. PMID:22378876

  1. Thyrotropin-releasing hormone (TRH) inhibits melanin-concentrating hormone neurons: implications for TRH-mediated anorexic and arousal actions.

    Science.gov (United States)

    Zhang, Xiaobing; van den Pol, Anthony N

    2012-02-29

    Thyrotropin-releasing hormone (TRH) increases activity and decreases food intake, body weight, and sleep, in part through hypothalamic actions. The mechanism of this action is unknown. Melanin-concentrating hormone (MCH) and hypocretin/orexin neurons in the lateral hypothalamus (LH) together with neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the arcuate nucleus play central roles in energy homeostasis. Here, we provide electrophysiological evidence from GFP-reporter transgenic mouse brain slices that shows TRH modulates the activity of MCH neurons. Using whole-cell current-clamp recording, we unexpectedly found that TRH and its agonist, montrelin, dose-dependently inhibited MCH neurons. Consistent with previous reports, TRH excited hypocretin/orexin neurons. No effect was observed on arcuate nucleus POMC or NPY neurons. The TRH inhibition of MCH neurons was eliminated by bicuculline and tetrodotoxin, suggesting that the effect was mediated indirectly through synaptic mechanisms. TRH increased spontaneous IPSC frequency without affecting amplitude and had no effect on miniature IPSCs or EPSCs. Immunocytochemistry revealed little interaction between TRH axons and MCH neurons, but showed TRH axons terminating on or near GABA neurons. TRH inhibition of MCH neurons was attenuated by Na(+)-Ca(2+) exchanger (NCX) inhibitors, TRPC channel blockers and the phospholipase C inhibitor U-73122. TRH excited LH GABA neurons, and this was also reduced by NCX inhibitors. Finally, TRH attenuated the excitation of MCH neurons by hypocretin. Together, our data suggest that TRH inhibits MCH neurons by increasing synaptic inhibition from local GABA neurons. Inhibition of MCH neurons may contribute to the TRH-mediated reduction in food intake and sleep.

  2. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

    Directory of Open Access Journals (Sweden)

    Mo Kyung Jung

    2014-12-01

    Full Text Available PurposeThere is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa in central precocious puberty (CPP. We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH in girls with CPP.MethodsWe reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS for bone age (BA, and compared adult height (AH with midparental height (MPH and predicted adult height (PAH during treatment in groups received GnRHa alone (n=59 or GnRHa plus GH (n=23.ResultsIn the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm was significantly higher than the initial PAH (156.6±3.96 cm (P<0.001, and it was similar to the MPH (159.9±3.52 cm. In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm was also higher than the initial PAH (154.6±2.55 cm (P<0.001, which was similar to the MPH (158.1±3.31 cm. Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.ConclusionIn CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

  3. Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation.

    Science.gov (United States)

    Everson, Carol A; Nowak, Thaddeus S

    2002-07-01

    Sleep deprivation in rats results in progressive declines in circulating concentrations of both total and free thyroxine (T(4)) and triiodothyronine (T(3)) without an expected increase in plasma thyroid-stimulating hormone (TSH). Administration of thyrotropin-releasing hormone (TRH) results in appropriate increases in plasma TSH, free T(4), and free T(3) across experimental days, suggesting deficient endogenous TRH production and/or release. This study examined transcriptional responses related to TRH regulation following sleep deprivation. In situ hybridization was used to detect and quantitate expression of mRNAs encoding prepro-TRH and 5'-deiodinase type II (5'-DII) in brain sections of six rats sleep deprived for 16-21 days, when there was marked hypothyroxinemia, and in sections from animals yoked to the experimental protocol as well as from sham controls. TRH transcript levels in the paraventricular nucleus (PVN) were essentially unchanged at 15-16 days but increased to about threefold control levels in three of four rats sleep deprived for 20-21 days, a change comparable to that typically found in prolonged experimental hypothyroidism. There was no evidence for suppression of 5'-DII mRNA levels, which would be a sign of T(3) feedback downregulation of neurons in the PVN. A failure to increase serum TSH in response to hypothyroxinemia and to increased prepro-TRH mRNA expression indicates that alterations in posttranscriptional stages of TRH synthesis, processing, or release likely mediate the central hypothyroidism induced by sleep deprivation.

  4. Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation.

    Science.gov (United States)

    Burnley, Brittney; P Jones, Harlan

    2017-01-01

    The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin-releasing hormone (CRH) is a neuropeptide released from the hypothalamic-pituitary-adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  5. Effects of Thyrotropin-Releasing Hormone (TRH) on the Actions of Pentobarbital and Other Centrally Acting Drugs1

    Science.gov (United States)

    Breese, George R.; Cott, Jerry M.; Cooper, Barrett R.; Prange, Arthur J.; Lipton, Morris A.; Plotnikoff, Nicholas P.

    2010-01-01

    Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or l-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital Studies of TRH analogs provided further support of this view In addition TRH reduced the sleep and hypothermia produced by thiopental amobarbital, seco-barbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus the results provide evidence that TRH acts on brain independent of an effect on the pituitary. PMID:805836

  6. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans.

    Science.gov (United States)

    Jayasena, Channa N; Nijher, Gurjinder M K; Comninos, Alexander N; Abbara, Ali; Januszewki, Adam; Vaal, Meriel L; Sriskandarajah, Labosshy; Murphy, Kevin G; Farzad, Zohreh; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

    2011-12-01

    Kisspeptin peptides are critical in human reproductive physiology and are potential therapies for infertility. Kisspeptin-10 stimulates gonadotropin release in both male and female rodents. However, few studies have investigated the effects of kisspeptin-10 on gonadotropin release in humans, and none have investigated the effect in women. If kisspeptin is to be useful for treating reproductive disease, its effects in both men and women must be established. To compare the effects of kisspeptin-10 administration on reproductive hormone release in healthy men and women. Intravenous bolus kisspeptin-10 was administered to men and women (n = 4-5 per group). Subcutaneous bolus and i.v. infusion of kisspeptin-10 was also administered to female women (n = 4-5 per group). Circulating reproductive hormones were measured. In healthy men, serum LH and FSH were elevated after i.v. bolus kisspeptin-10, at doses as low as 0.3 and 1.0 nmol/kg, respectively. In healthy women during the follicular phase of the menstrual cycle, no alterations in serum gonadotropins were observed after i.v. bolus, s.c. bolus, or i.v. infusion of kisspeptin-10 at maximal doses of 10 nmol/kg, 32 nmol/kg, and 720 pmol/kg/min, respectively. In women during the preovulatory phase, serum LH and FSH were elevated after i.v. bolus kisspeptin-10 (10 nmol/kg). Kisspeptin-10 stimulates gonadotropin release in men as well as women during the preovulatory phase of menstrual cycle but fails to stimulate gonadotropin release in women during the follicular phase. The sexual dimorphism of the responsiveness of healthy men and women to kisspeptin-10 administration has important clinical implications for the potential of kisspeptin-10 to treat disorders of reproduction.

  7. Central corticotropin releasing factor and social stress.

    Science.gov (United States)

    Backström, Tobias; Winberg, Svante

    2013-01-01

    Social interactions are a main source of stress in vertebrates. Social stressors, as well as other stressors, activate the hypothalamic-pituitary-adrenal (HPA) axis resulting in glucocorticoid release. One of the main components of the HPA axis is corticotropin releasing factor (CRF). The neuropeptide CRF is part of a peptide family including CRF, urocortin 1-3, urotensin 1-3, and sauvagine. The actions of the CRF family are mediated by at least two different receptors with different anatomical distribution and affinities for the peptides. The CRF peptides affect several behavioral and physiological responses to stress including aggression, feeding, and locomotor activity. This review will summarize recent research in vertebrates concerning how social stress interacts with components of the CRF system. Consideration will be taken to the different models used for social stress ranging from social isolation, dyadic interactions, to group dominance hierarchies. Further, the temporal effect of social stressor from acute, intermittent, to chronic will be considered. Finally, strains selected for specific behavior or physiology linked to social stress will also be discussed.

  8. Central corticotropin releasing factor and social stress

    Directory of Open Access Journals (Sweden)

    Tobias eBackström

    2013-07-01

    Full Text Available Social interactions are a main source of stress in vertebrates. Social stressors, as well as other stressors, activate the hypothalamic-pituitary-adrenal (HPA axis resulting in glucocorticoid release. One of the main components of the HPA axis is corticotropin releasing factor (CRF. The neuropeptide CRF is part of a peptide family including CRF, urocortin 1-3, urotensin 1-3 and sauvagine. The actions of the CRF family are mediated by at least two different receptors with different anatomical distribution and affinities for the peptides. The CRF peptides affect several behavioral and physiological responses to stress including aggression, feeding and locomotor activity. This review will summarize recent research in vertebrates concerning how social stress interacts with components of the CRF system. Consideration will be taken to the different models used for social stress ranging from social isolation, dyadic interactions, to group dominance hierarchies. Further, the temporal effect of social stressor from acute, intermittent, to chronic will be considered. Finally, strains selected for specific behavior or physiology linked to social stress will also be discussed.

  9. Levels of the epidermal growth factor-like peptide amphiregulin in follicular fluid reflect the mode of triggering ovulation: a comparison between gonadotrophin-releasing hormone agonist and urinary human chorionic gonadotrophin

    DEFF Research Database (Denmark)

    Humaidan, Peter; Westergaard, Lars Grabow; Mikkelsen, Anne Lis

    2011-01-01

    . INTERVENTION(S): Ovulation triggered with either urinary hCG or GnRH agonist (GnRH-a). Controls: 15 FF samples from small antral follicles (3-9 mm) and 12 FF samples from natural cycle. MAIN OUTCOME MEASURE(S): Follicular fluid concentration of AR, P(4), E(2), vascular endothelial growth factor, and inhibin B...

  10. Regulation of gonadotropins by corticotropin-releasing factor and urocortin

    Directory of Open Access Journals (Sweden)

    Kazunori eKageyama

    2013-02-01

    Full Text Available While stress activates the hypothalamic-pituitary-adrenal (HPA axis, it suppresses the hypothalamic-pituitary-gonadal (HPG axis. Corticotropin-releasing factor (CRF is a major regulatory peptide in the HPA axis during stress. Urocortin1 (Ucn1, a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF2 receptor. The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF2 receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  11. Regulation of gonadotropins by corticotropin-releasing factor and urocortin.

    Science.gov (United States)

    Kageyama, Kazunori

    2013-01-01

    While stress activates the hypothalamic-pituitary-adrenal (HPA) axis, it suppresses the hypothalamic-pituitary-gonadal (HPG) axis. Corticotropin-releasing factor (CRF) is a major regulatory peptide in the HPA axis during stress. Urocortin 1 (Ucn1), a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF(2) receptor). The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH) via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF(2) receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  12. Thyroid hormone promotes transient nerve growth factor synthesis in rat cerebellar neuroblasts.

    Science.gov (United States)

    Charrasse, S; Jehan, F; Confort, C; Brachet, P; Clos, J

    1992-01-01

    Primary cultures of cerebellum from 5-day-old rats indicated that proliferating neuroblasts synthesize and release nerve growth factor (NGF). Since NGF promotes DNA synthesis in these cells, our findings demonstrate that the early developing cerebellum is a suitable physiological model for studying the autocrine mitogenic action of NGF. Thyroid deficiency led to a greater reduction in the NGF content of the cerebellum than of the olfactory bulbs or hippocampus. Cerebellar NGF mRNA was also very sensitive to hormone deprivation. Physiological amounts of thyroid hormone stimulated both the mitotic activity and NGF production of cultured cerebellar neuroblasts. A lack of thyroid hormone is known to markedly alter cell formation in the cerebellum where postnatal neurogenesis is highly significant, in contrast to the olfactory bulbs and hippocampus. Taken together, these results suggest that the hormonal control of cell formation in the cerebellum is, at least partly, mediated by the autocrine mitogenic action of NGF. The thyroid hormone could temporally regulate the transient NGF synthesis by cerebellar neuroblasts directly and/or through its ontogenetic action, and hence all the NGF-dependent trophic effects.

  13. Evidence that locustatachykinin I is involved in release of adipokinetic hormone from locust corpora cardiaca.

    Science.gov (United States)

    Nässel, D R; Passier, P C; Elekes, K; Dircksen, H; Vullings, H G; Cantera, R

    1995-06-27

    The glandular cells of the corpus cardiacum of the locust Locusta migratoria, known to synthesize and release adipokinetic hormones (AKH), are contacted by axons immunoreactive to an antiserum raised against the locust neuropeptide locustatachykinin I (LomTK I). Electron-microscopical immunocytochemistry reveals LomTK immunoreactive axon terminals, containing granular vesicles, in close contact with the glandular cells cells. Release of AKH I from isolated corpora cardiaca of the locust has been monitored in an in vitro system where the amount of AKH I released into the incubation saline is determined by reversed phase high performance liquid chromatography with fluorometric detection. We could show that LomTK I induces release of AKH from corpora cardiaca in a dose-dependent manner when tested in a range of 10-200 microM. This is thus the first clear demonstration of a substance inducing release of AKH, correlated with the presence of the substance in fibers innervating the AKH-synthesizing glandular cells, in the insect corpora cardiaca.

  14. Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin-Releasing Hormone (TRH) Analogues

    OpenAIRE

    Monga, Vikramdeep; Meena, Chhuttan L.; Rajput, Satyendra; Pawar, Chandrashekhar; Shyam S. Sharma; Lu, Xinping; Gershengorn, Marvin C.; Jain, Rahul

    2011-01-01

    As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 ...

  15. Parathyroid hormone stimulates juxtaglomerular cell cAMP accumulation without stimulating renin release

    Science.gov (United States)

    Atchison, Douglas K.; Harding, Pamela; Cecilia Ortiz-Capisano, M.; Peterson, Edward L.

    2012-01-01

    Parathyroid hormone (PTH) is positively coupled to the generation of cAMP via its actions on the PTH1R and PTH2R receptors. Renin secretion from juxtaglomerular (JG) cells is stimulated by elevated intracellular cAMP, and every stimulus that increases renin secretion is thought to do so via increasing cAMP. Thus we hypothesized that PTH increases renin release from primary cultures of mouse JG cells by elevating intracellular cAMP via the PTH1R receptor. We found PTH1R, but not PTH2R, mRNA expressed in JG cells. While PTH increased JG cell cAMP content from (log10 means ± SE) 3.27 ± 0.06 to 3.92 ± 0.12 fmol/mg protein (P renin release. The PTH1R-specific agonist, parathyroid hormone-related protein (PTHrP), also increased JG cell cAMP from 3.13 ± 0.09 to 3.93 ± 0.09 fmol/mg protein (P renin release. PTH2R receptor agonists had no effect on cAMP or renin release. PTHrP increased cAMP in the presence of both low and high extracellular calcium from 3.31 ± 0.17 to 3.83 ± 0.20 fmol/mg protein (P renin release. PTHrP increased JG cell cAMP in the presence of adenylyl cyclase-V inhibition from 2.85 ± 0.17 to 3.44 ± 0.14 fmol/mg protein (P renin release. As a positive control, forskolin increased JG cell cAMP from 3.39 ± 0.13 to 4.48 ± 0.07 fmol/mg protein (P renin release from 2.96 ± 0.10 to 3.29 ± 0.08 ng ANG I·mg prot−1·h−1 (P renin release. These data suggest compartmentalization of cAMP signaling in JG cells. PMID:22896038

  16. 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, ...

  17. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children.

    Science.gov (United States)

    Cicchetti, Dante; Rogosch, Fred A

    2014-11-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition, BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1

  18. Anthropometric and hormonal risk factors for male breast cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

    -control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. RESULTS: Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1......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 consortium.......41; 95% CI = 1.07 to 1.86). CONCLUSIONS: Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles...

  19. The dopaminergic regulation of gonadotropin-releasing hormone receptor binding in the pituitary of the African catfish, Clarias gariepinus

    NARCIS (Netherlands)

    de Leeuw, R.; van 't Veer, C.; Goos, H. J.; van Oordt, P. G.

    1988-01-01

    In several teleost species, including the African catfish, dopamine acts as an endogenous inhibitor of gonadotropin-releasing hormone (GnRH)-stimulated gonadotropin (GTH) release. The present in vivo study was carried out to investigate whether this inhibitory action of dopamine can be explained by

  20. Activation of arcuate nucleus neurons by systemic administration of leptin and growth hormone-releasing peptide-6 in normal and fasted rats.

    Science.gov (United States)

    Luckman, S M; Rosenzweig, I; Dickson, S L

    1999-08-01

    Both leptin and growth hormone secretagogues are believed to have stimulatory effects on the hypothalamic growth hormone pulse generator, though whether these are achieved through the same pathway is unknown. Systemic administration of a normally maximal effective dose of the growth hormone secretagogue GHRP-6 to male rats causes the induction of c-Fos protein in the ventromedial aspect of the hypothalamic arcuate nucleus. The effect of the same dose of GHRP-6 is, however, much greater in animals that have been fasted for 48 h, suggesting that in the food-replete rat, arcuate neurons either show reduced sensitivity to endogenous growth hormone secretagogues or they are under the tonic inhibitory influences of other factors. The major populations of arcuate neurons activated by GHRP-6 have been shown to contain neuropeptide Y or growth hormone-releasing factor, while leptin is thought to be inhibitory to neuropeptide Y neurons. Leptin did not alter the response of the rats to GHRP-6. However, it was able by itself to induce c-Fos protein immunoreactivity in the ventral, including the ventrolateral, arcuate nucleus of fasted rats. This is a clear demonstration of the acute activation of arcuate neurons in the rat following systemic leptin injection and suggests that GHRP-6 and leptin act on the growth hormone axis via different pathways.

  1. Injection of corticotropin-releasing hormone into the amygdala aggravates visceral nociception and induces noradrenaline release in rats.

    Science.gov (United States)

    Su, J; Tanaka, Y; Muratsubaki, T; Kano, M; Kanazawa, M; Fukudo, S

    2015-01-01

    Corticotropin-releasing hormone (CRH) and its receptor 1 (CRH-R1) play an important role in the colonic response to stress. The central nucleus of the amygdala (CeA) is a major extrahypothalamic site that contains a large number of neurons expressing both CRH and CRH-R1. Here, we verified the hypothesis that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline, dopamine, and serotonin (5-HT) in the CeA. In male Wistar rats, visceral sensitivity was quantified by recording the visceromotor response to colorectal distension (CRD) with administration of vehicle, CRH, or the CRH-R1 antagonist CP-154526+ CRH or CRH-R1 antagonist CP-154526 alone into the CeA. Simultaneously, extracellular levels of noradrenaline, dopamine, and 5-HT were measured in the CeA using microdialysis. All data were obtained under restraint conditions. Administration of CRH into the CeA significantly increased the number of abdominal muscle contractions in response to CRD. CP-154526 significantly blocked the number of abdominal muscle contractions in response to CRD with the administration of CRH into the CeA. Noradrenaline in the CeA was increased by CRD, further increased by CRH, and inhibited by CRH-R1 antagonist. Dopamine in the CeA was also exaggerated by CRH but was not inhibited by CRH-R1 antagonist. 5-HT in the CeA was unchanged. These results suggest that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline. © 2014 John Wiley & Sons Ltd.

  2. Multiple genetic factors in the heterogeneity of thyroid hormone resistance

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, R.E.; Refetoff, S. (Univ. of Chicago, IL (United States)); Marcocci, C.; Bruno-Bossio, G. (Univ. of Pisa (Italy))

    1993-01-01

    Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T[sub 3]-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR[beta] mutations have been reported. The authors compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T[sub 3]-binding domain of TR[beta]; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR[beta] mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T[sub 4] and T[sub 3], and rT[sub 3] levels were significantly higher in Group A vs Groups B and C. However, with the exception of T[sub 3], the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR[beta] mutations. 23 refs., 2 figs., 1 tab.

  3. Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH neurons

    Directory of Open Access Journals (Sweden)

    Christian Cortés-Campos

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.

  4. Internalization and recycling of receptor-bound gonadotropin-releasing hormone agonist in pituitary gonadotropes

    Energy Technology Data Exchange (ETDEWEB)

    Schvartz, I.; Hazum, E.

    1987-12-15

    The fate of cell surface gonadotropin-releasing hormone (GnRH) receptors on pituitary cells was studied utilizing lysosomotropic agents and monensin. Labeling of pituitary cells with a photoreactive GnRH derivative, (azidobenzoyl-D-Lys6)GnRH, revealed a specific band of Mr = 60,000. When photoaffinity-labeled cells were exposed to trypsin immediately after completion of the binding, the radioactivity incorporated into the Mr = 60,000 band decreased, with a concomitant appearance of a proteolytic fragment (Mr = 45,000). This fragment reflects cell surface receptors. Following GnRH binding, the hormone-receptor complexes underwent internalization, partial degradation, and recycling. The process of hormone-receptor complex degradation was substantially prevented by lysosomotropic agents, such as chloroquine and methylamine, or the proton ionophore, monensin. Chloroquine and monensin, however, did not affect receptor recycling, since the tryptic fragment of Mr = 45,000 was evident after treatment with these agents. This suggests that recycling of GnRH receptors in gonadotropes occurs whether or not the internal environment is acidic. Based on these findings, we propose a model describing the intracellular pathway of GnRH receptors.

  5. Molecular analysis of the koala reproductive hormones and their receptors: gonadotrophin-releasing hormone (GnRH), follicle-stimulating hormone β and luteinising hormone β with localisation of GnRH.

    Science.gov (United States)

    Busby, E R; Soeta, S; Sherwood, N M; Johnston, S D

    2014-12-01

    During evolution, reproductive hormones and their receptors in the brain-pituitary-gonadal axis have been altered by genetic mechanisms. To understand how the neuroendocrine control of reproduction evolved in mammals, it is important to examine marsupials, the closest group to placental mammals. We hypothesised that at least some of the hormones and receptors found in placental mammals would be present in koala, a marsupial. We examined the expression of koala mRNA for the reproductive molecules. Koala cDNAs were cloned from brain for gonadotrophin-releasing hormones (GnRH1 and GnRH2) or from pituitary for GnRH receptors, types I and II, follicle-stimulating hormone (FSH)β and luteinising hormone (LH)β, and from gonads for FSH and LH receptors. Deduced proteins were compared by sequence alignment and phylogenetic analysis with those of other vertebrates. In conclusion, the koala expressed mRNA for these eight putative reproductive molecules, whereas at least one of these molecules is missing in some species in the amniote lineage, including humans. In addition, GnRH1 and 2 are shown by immunohistochemistry to be expressed as proteins in the brain. © 2014 British Society for Neuroendocrinology.

  6. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates.

    Science.gov (United States)

    Minakata, Hiroyuki

    2010-07-01

    Recent advances in peptide search methods have revealed two peptide systems that have been conserved through metazoan evolution. Members of the oxytocin/vasopressin-superfamily have been identified from protostomian and deuterostomian animals, indicating that the oxytocin/vasopressin hormonal system represents one of the most ancient systems. In most protostomian animals, a single member of the superfamily shares oxytocin-like and vasopressin-like actions. Co-occurrence of two members has been discovered in modern cephalopods, octopus, and cuttlefish. We propose that cephalopods have developed two peptides in the molluscan evolutionary lineage like vertebrates have established two lineages in the oxytocin/vasopressin superfamily. The existence of gonadotropin-releasing hormone (GnRH) in protostomian animals was initially suggested by immunohistochemical analysis using chordate GnRH antibodies. A peptide with structural features similar to those of chordate GnRHs was originally isolated from octopus, and an identical peptide has been characterized from squid and cuttlefish. Novel forms of GnRH-like molecules from other molluscs, an annelid, arthropods, and nematodes demonstrate somewhat conserved structures at the N-terminal regions; but structures of the C-terminal regions critical to gonadotropin-releasing activity are diverse. These findings may be important for the study of the molecular evolution of GnRH in protostomian animals.

  7. Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs.

    Science.gov (United States)

    Monga, Vikramdeep; Meena, Chhuttan L; Kaur, Navneet; Jain, Rahul

    2008-01-01

    Thyrotropin-releasing hormone (TRH), a hypothalamic orally active neuropeptide, has been manifested in a wide range of biological responses. Besides its central role in regulating the pituitary-thyroid axis by simulating the release of thyrotropin, TRH has considerable influence on the activity of a number of neurobiological systems. Due to the therapeutic potential of TRH to treat several CNS maladies, the development of CNS-selective and metabolically stable TRH analogs is an area of interest. TRH is known to elicit its biological response through two G-protein coupled receptors for TRH (namely, TRH-R1 and TRH-R2). The distinct distribution of TRH receptors in tissues has provided opportunity to discover receptor subtype-specific analogs, which would demonstrate high CNS activities, and are completely free of hormonal activities. In this review, an in-depth analysis of the chemistry and biology of TRH and its analogs is provided. Recent discoveries of TRH-R2 selective analogs, TRH super agonists, metabolically stable TRH analogs, and targeted delivery of TRH analogs have been also discussed.

  8. Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.

    Science.gov (United States)

    Maeng, L Y; Taha, M B; Cover, K K; Glynn, S S; Murillo, M; Lebron-Milad, K; Milad, M R

    2017-08-01

    Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Persistent signaling by thyrotropin-releasing hormone receptors correlates with G-protein and receptor levels

    Science.gov (United States)

    Boutin, Alisa; Allen, Michael D.; Neumann, Susanne; Gershengorn, Marvin C.

    2012-01-01

    G-protein-coupled receptors with dissociable agonists for thyrotropin, parathyroid hormone, and sphingosine-1-phosphate were found to signal persistently hours after agonist withdrawal. Here we show that mouse thyrotropin-releasing hormone (TRH) receptors, subtypes 2 and 1(TRH-R2 and TRH-R1), can signal persistently in HEK-EM293 cells under appropriate conditions, but TRH-R2 exhibits higher persistent signaling activity. Both receptors couple primarily to Gαq/11. To gain insight into the mechanism of persistent signaling, we compared proximal steps of inositolmonophosphate (IP1) signaling by TRH-Rs. Persistent signaling was not caused by slower dissociation of TRH from TRH-R2 (t1/2=77±8.1 min) compared with TRH-R1 (t1/2=82±12 min) and was independent of internalization, as inhibition of internalization did not affect persistent signaling (115% of control), but required continuously activated receptors, as an inverse agonist decreased persistent signaling by 60%. Gαq/11 knockdown decreased persistent signaling by TRH-R2 by 82%, and overexpression of Gαq/11 induced persistent signaling in cells expressing TRH-R1. Lastly, persistent signaling was induced in cells expressing high levels of TRH-R1. We suggest that persistent signaling by TRHRs is exhibited when sufficient levels of agonist/receptor/G-protein complexes are established and maintained and that TRH-R2 forms and maintains these complexes more efficiently than TRH-R1.—Boutin, A., Allen, M. D., Neumann, S., Gershengorn, M. C. Persistent signaling by thyrotropin-releasing hormone receptors correlates with G-protein and receptor levels. PMID:22593547

  10. [Effects of gonadotropin releasing hormone analog and growth hormone on height in girls with idiopathic central precocious puberty].

    Science.gov (United States)

    Wang, Chun-Lin; Liang, Li; Liu, Pei-Ning; Jin, Xian-Jiang; Chen, Lin-Qi; Yang, Fang; Lian, Qun; Chen, Rui-Min

    2014-01-01

    To determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP). Eighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 ±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03 ±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups. HtSDS-BA was significantly improved after treatment for both groups (Padult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant. Both GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.

  11. Milk minor constituents, enzymes, hormones, growth factors, and organic acids

    OpenAIRE

    RODRIGUES L. R.

    2013-01-01

    Milk and derived products contain essential nutrients, such as proteins, lactose, minerals, vitamins, and enzymes. Additionally, despite of their low concentrations in milk, many other minor constituents present important physiological and/or technological roles (e.g. hormones, growth factors). Dairy industries face many challenges regarding milk processing. Also, the full knowledge on these constituents’ physiological roles and effects on health is still lacking. Technological...

  12. Apoptotic death of prostate cancer cells by a gonadotropin-releasing hormone-II antagonist.

    Directory of Open Access Journals (Sweden)

    Sumi Park

    Full Text Available Gonadotropin-releasing hormone-I (GnRH-I has attracted strong attention as a hormonal therapeutic tool, particularly for androgen-dependent prostate cancer patients. However, the androgen-independency of the cancer in advanced stages has spurred researchers to look for new medical treatments. In previous reports, we developed the GnRH-II antagonist Trp-1 to inhibit proliferation and stimulate the autophagic death of various prostate cancer cells, including androgen-independent cells. We further screened many GnRH-II antagonists to identify molecules with higher efficiency. Here, we investigated the effect of SN09-2 on the growth of PC3 prostate cancer cells. SN09-2 reduced the growth of prostate cancer cells but had no effect on cells derived from other tissues. Compared with Trp-1, SN09-2 conspicuously inhibited prostate cancer cell growth, even at low concentrations. SN09-2-induced PC3 cell growth inhibition was associated with decreased membrane potential in mitochondria where the antagonist was accumulated, and increased mitochondrial and cytosolic reactive oxygen species. SN09-2 induced lactate dehydrogenase release into the media and annexin V-staining on the PC3 cell surface, suggesting that the antagonist stimulated prostate cancer cell death by activating apoptotic signaling pathways. Furthermore, cytochrome c release from mitochondria to the cytosol and caspase-3 activation occurred in a concentration- and time-dependent manner. SN09-2 also inhibited the growth of PC3 cells xenotransplanted into nude mice. These results demonstrate that SN09-2 directly induces mitochondrial dysfunction and the consequent ROS generation, leading to not only growth inhibition but also apoptosis of prostate cancer cells.

  13. The thyrotropin-releasing hormone (TRH)-immune system homeostatic hypothesis.

    Science.gov (United States)

    Kamath, J; Yarbrough, G G; Prange, A J; Winokur, A

    2009-01-01

    Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics. J Pharmacol Exp Ther 305(2):410-416.] and Yarbrough et al. [Yarbrough, G.G., Kamath, J., Winokur, A., Prange, A.J. Jr. (2007). Thyrotropin-releasing hormone (TRH) in the neuroaxis: therapeutic effects reflect physiological functions and molecular actions. Med Hypotheses 69(6):1249-1256.] provided a functional framework, predicated on its global homeostatic influences, to conceptualize the numerous interactions of TRH with the central nervous system (CNS) and endocrine system. Herein, we profer a similar analysis to interactions of TRH with the immune system. Autocrine/paracrine cellular signaling motifs of TRH and TRH receptors are expressed in several tissues and organs of the immune system. Consistent with this functional distribution, in vitro and in vivo evidence suggests a critical role for TRH during the developmental stages of the immune system as well as its numerous interactions with the fully developed immune system. Considerable evidence supports a pivotal role for TRH in the pathophysiology of the inflammatory process with specific relevance to the "cytokine-induced sickness behavior" paradigm. These findings, combined with a number of documented clinical actions of TRH strongly support a potential utility of TRH-based therapeutics in select inflammatory disorders. Similar to its global role in behavioral and energy homeostasis a homeostatic role for TRH in its interactions with the immune system is consonant with the large body of available data. Recent advances in the field of immunology provide a significant opportunity for investigation of the TRH

  14. Effects of growth hormone-releasing hormone on sleep and brain interstitial fluid amyloid-β in an APP transgenic mouse model.

    Science.gov (United States)

    Liao, Fan; Zhang, Tony J; Mahan, Thomas E; Jiang, Hong; Holtzman, David M

    2015-07-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive function, extracellular amyloid plaques, intracellular neurofibrillary tangles, and synaptic and neuronal loss. There is substantial evidence that the aggregation of amyloid β (Aβ) in the brain plays a key role in the pathogenesis of AD and that Aβ aggregation is a concentration dependent process. Recently, it was found that Aβ levels in the brain interstitial fluid (ISF) are regulated by the sleep-wake cycle in both humans and mice; ISF Aβ is higher during wakefulness and lower during sleep. Intracerebroventricular infusion of orexin increased wakefulness and ISF Aβ levels, and chronic sleep deprivation significantly increased Aβ plaque formation in amyloid precursor protein transgenic (APP) mice. Growth hormone-releasing hormone (GHRH) is a well-documented sleep regulatory substance which promotes non-rapid eye movement sleep. GHRHR(lit/lit) mice that lack functional GHRH receptor have shorter sleep duration and longer wakefulness during light periods. The current study was undertaken to determine whether manipulating sleep by interfering with GHRH signaling affects brain ISF Aβ levels in APPswe/PS1ΔE9 (PS1APP) transgenic mice that overexpress mutant forms of APP and PSEN1 that cause autosomal dominant AD. We found that intraperitoneal injection of GHRH at dark onset increased sleep and decreased ISF Aβ and that delivery of a GHRH antagonist via reverse-microdialysis suppressed sleep and increased ISF Aβ. The diurnal fluctuation of ISF Aβ in PS1APP/GHRHR(lit/lit) mice was significantly smaller than that in PS1APP/GHRHR(lit/+) mice. However despite decreased sleep in GHRHR deficient mice, this was not associated with an increase in Aβ accumulation later in life. One of several possibilities for the finding is the fact that GHRHR deficient mice have GHRH-dependent but sleep-independent factors which protect against Aβ deposition. Copyright © 2014

  15. Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea.

    Science.gov (United States)

    Jayasena, C N; Nijher, G M K; Abbara, A; Murphy, K G; Lim, A; Patel, D; Mehta, A; Todd, C; Donaldson, M; Trew, G H; Ghatei, M A; Bloom, S R; Dhillo, W S

    2010-12-01

    Kisspeptin is a novel therapeutic target for infertility. A single kisspeptin-54 (KP-54) injection acutely stimulates the release of reproductive hormones in women with hypothalamic amenorrhea (HA), a commonly occurring condition characterized by absence of menstruation; however, twice-daily administration of KP-54 results in tachyphylaxis. We determined the time course of desensitization to twice-daily KP-54 injections, compared the effects of twice-daily and twice-weekly administration regimens of KP-54, and studied the effects of long-term twice-weekly administration of KP-54 on the release of reproductive hormones in women with HA. When KP-54 was administered twice daily, responsiveness to luteinizing hormone (LH) diminished gradually, whereas responsiveness to follicle-stimulating hormone (FSH) was nearly abolished by day 2. Twice-weekly KP-54 administration resulted in only partial desensitization, in contrast to the complete tolerance achieved with twice-daily administration. Women with HA who were treated with twice-weekly KP-54 injections had significantly elevated levels of reproductive hormones after 8 weeks as compared with treatment with saline. No adverse effects were observed. This study provides novel pharmacological data on the effects of KP-54 on the release of reproductive hormones in women with HA.

  16. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleost...

  17. Impairment of Host Liver Repopulation by Transplanted Hepatocytes in Aged Rats and the Release by Short-Term Growth Hormone Treatment.

    Science.gov (United States)

    Stock, Peggy; Bielohuby, Maximilian; Staege, Martin S; Hsu, Mei-Ju; Bidlingmaier, Martin; Christ, Bruno

    2017-03-01

    Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, efficient liver repopulation by transplanted hepatocytes is low in livers of old animals. This restraint might be because of the poor proliferative capacity of aged donor hepatocytes or the regenerative impairment of the recipient livers. The age-dependent liver repopulation by transplanted wild-type hepatocytes was investigated in juvenile and senescent rats deficient in dipeptidyl-peptidase IV. Repopulation was quantified by flow cytometry and histochemical estimation of dipeptidyl-peptidase IV enzyme activity of donor cells in the negative host liver. As a potential pathway involved, expression of cell cycle proteins was assessed. Irrespective of the age of the donor hepatocytes, large cell clusters appeared in juvenile, but only small clusters in senescent host livers. Because juvenile and senescent donor hepatocytes were likewise functional, host-derived factor(s) impaired senescent host liver repopulation. Growth hormone levels were significantly higher in juvenile than in senescent rats, suggesting that growth hormone might promote host liver repopulation. Indeed, short-term treatment with growth hormone augmented senescent host liver repopulation involving the growth hormone-mediated release of the transcriptional blockade of genes associated with cell cycle progression. Short-term growth hormone substitution might improve liver repopulation by transplanted hepatocytes, thus augmenting the therapeutic benefit of clinical hepatocyte transplantation in older patients. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.

    Directory of Open Access Journals (Sweden)

    Stefan Lim

    Full Text Available The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta and follicle-stimulating hormone beta-subunit (FSHbeta. Three mitogen-activated protein kinases, (MAPKs, ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R. Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.

  19. Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

    Science.gov (United States)

    Thirunarayanan, Nanthakumar; Raaka, Bruce M.; Gershengorn, Marvin C.

    2012-01-01

    Taltirelin (TAL) is a thyrotropin-releasing hormone (TRH) analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R) in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating central nervous system effects in humans compared to TRH. PMID:23087672

  20. Pituitary Apoplexy After Thyrotropin-releasing Hormone Stimulation Test in a Patient with Pituitary Macroadenoma

    Directory of Open Access Journals (Sweden)

    Huei-Fang Wang

    2007-09-01

    Full Text Available Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH 200 mg intravenous injection stimulation test. Neither emergency computed tomography (CT scans nor magnetic resonance imaging (MRI, performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

  1. Regulation of the Hypothalamic Thyrotropin Releasing Hormone (TRH) Neuron by Neuronal and Peripheral Inputs

    Science.gov (United States)

    Nillni, Eduardo A.

    2010-01-01

    The hypothalamic pituitary thyroid (HPT) axis plays a critical role in mediating changes in metabolism and thermogenesis. Thus, the central regulation of the thyroid axis by Thyrotropin Releasing Hormone (TRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) is of key importance for the normal function of the axis under different physiological conditions including cold stress and changes in nutritional status. Before the TRH peptide becomes biologically active, a series of tightly regulated processes occur including the proper folding of the prohormone for targeting to the secretory pathway, its post-translational processing, and targeting of the processed peptides to the secretory granules near the plasma membrane of the cell ready for secretion. Multiple inputs coming from the periphery or from neurons present in different areas of the brain including the hypothalamus are responsible for the activation or inhibition of the TRH neuron and in turn affect the output of TRH and the set point of the axis. PMID:20074584

  2. Interaction between thyrotropin-releasing hormone (TRH) and NMDA-receptor-mediated responses in hypoglossal motoneurones

    DEFF Research Database (Denmark)

    Rekling, J C

    1992-01-01

    The effect of thyrotropin-releasing hormone (TRH) on the responses to excitatory amino acids was investigated in hypoglossal motoneurones in an in vitro preparation of the brainstem from guinea pigs using current clamp and discontinuous single electrode voltage clamp (dSEVC). Bath application of 20......-50 microM TRH markedly potentiated the response to iontophoretically applied NMDA, whereas no potentiation of the response to glutamate, aspartate or quisqualic acid was seen. Voltage clamp experiments showed that TRH did not increase the current flowing through NMDA channels, thus a direct modulatory role...... of TRH on NMDA channels was not a likely explanation of the potentiation. Voltage clamp studies of the current-voltage relationship showed that the potentiation of the response to NMDA and lack of potentiation of the response to quisqualic acid was a result of an interaction between the actions of TRH...

  3. Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor

    Directory of Open Access Journals (Sweden)

    Nanthakumar eThirunarayanan

    2012-10-01

    Full Text Available Taltirelin (TAL is a thyrotropin-releasing hormone (TRH analog that is approved for use in humans in Japan. In this study, we characterized TAL binding to and signaling by the human TRH receptor (TRH-R in a model cell system. We found that TAL exhibited lower binding affinities than TRH and lower signaling potency via the inositol-1,4,5-trisphosphate/calcium pathway than TRH. However, TAL exhibited higher intrinsic efficacy than TRH in stimulating inositol-1,4,5-trisphosphate second messenger generation. This is the first study that elucidates the pharmacology of TAL at TRH-R and shows that TAL is a superagonist at TRH-R. We suggest the superagonism exhibited by TAL may in part explain its higher activity in mediating CNS effects in humans compared to TRH.

  4. Enzymatic tracer damage during the gonadotropin releasing hormone radioimmunoassay: analytical and immunological assessment

    Energy Technology Data Exchange (ETDEWEB)

    O' Conner, J.L.; Lapp, C.A.; Clary, A.R.

    1985-09-23

    Hypothalamic supernatants from 60 day female rats were fractionated from Sephadex G-200 columns. The radioimmunoassay (RIA) for gonadotropin releasing hormone (GnRH) detected an apparently cross-reacting high molecular weight substance. The substance caused apparent displacement of iodinated GnRH binding in dose response fashion; however, no biological activity was observed in pituitary cell cultures. In order to determine whether the depressed binding might be caused by enzymatic degradation of iodinated GnRH during the RIA incubation, iodinated GnRH was preincubated under RIA conditions with either buffer or increasing concentrations of the GnRH cross-reacting material. Aliquots were subjected to polyacrylamide gel electrophoresis (PAGE) and the gels slices counted. Identical aliquots were subsequently used as iodinated hormone in the RIA of known quantities of synthetic GnRH. Tracer damage during the RIA-like preincubation period was reflected in the subsequent PAGE studies as decreased counts per minute in the intact GnRH peak and in the RIA studies as over-estimated quantification of the GnRH standards. This report describes such damage during the GnRH RIA and the data misinterpretations which result. 30 references, 6 figures, 1 table.

  5. Thyrotropin releasing hormone (TRH): a new player in human hair-growth control.

    Science.gov (United States)

    Gáspár, Erzsébet; Hardenbicker, Celine; Bodó, Eniko; Wenzel, Björn; Ramot, Yuval; Funk, Wolfgang; Kromminga, Arno; Paus, Ralf

    2010-02-01

    Thyrotropin-releasing hormone (TRH) is the most proximal component of the hypothalamic-pituitary-thyroid axis that regulates thyroid hormone synthesis. Since transcripts for members of this axis were detected in cultured normal human skin cells and since human hair follicles (HFs) respond to stimulation with thyrotropin, we now have studied whether human HF functions are also modulated by TRH. Here we report that the epithelium of normal human scalp HFs expresses not only TRH receptors (TRH-R) but also TRH itself at the gene and protein level. Stimulation of microdissected, organ-cultured HFs with TRH promotes hair-shaft elongation, prolongs the hair cycle growth phase (anagen), and antagonizes its termination by TGF-beta2. It also increases proliferation and inhibits apoptosis of hair matrix keratinocytes. These TRH effects may be mediated in part by reducing the ATM/Atr-dependent phosphorylation of p53. By microarray analysis, several differentially up- or down-regulated TRH-target genes were detected (e.g., selected keratins). Thus, human scalp HFs are both a source and a target of TRH, which operates as a potent hair-growth stimulator. Human HFs provide an excellent discovery tool for identifying and dissecting nonclassical functions of TRH and TRH-mediated signaling in situ, which emerge as novel players in human epithelial biology.

  6. Family members CREB and CREM control thyrotropin-releasing hormone (TRH) expression in the hypothalamus.

    Science.gov (United States)

    Chiappini, Franck; Ramadoss, Preeti; Vella, Kristen R; Cunha, Lucas L; Ye, Felix D; Stuart, Ronald C; Nillni, Eduardo A; Hollenberg, Anthony N

    2013-01-05

    Thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus is regulated by thyroid hormone (TH). cAMP response element binding protein (CREB) has also been postulated to regulate TRH expression but its interaction with TH signaling in vivo is not known. To evaluate the role of CREB in TRH regulation in vivo, we deleted CREB from PVN neurons to generate the CREB1(ΔSIM1) mouse. As previously shown, loss of CREB was compensated for by an up-regulation of CREM in euthyroid CREB1(ΔSIM1) mice but TSH, T₄ and T₃ levels were normal, even though TRH mRNA levels were elevated. Interestingly, TRH mRNA expression was also increased in the PVN of CREB1(ΔSIM1) mice in the hypothyroid state but became normal when made hyperthyroid. Importantly, CREM levels were similar in CREB1(ΔSIM1) mice regardless of thyroid status, demonstrating that the regulation of TRH by T₃ in vivo likely occurs independently of the CREB/CREM family. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Leptin "gates" thermogenic action of thyrotropin-releasing hormone in the hindbrain.

    Science.gov (United States)

    Rogers, Richard C; Barnes, Maria J; Hermann, Gerlinda E

    2009-10-27

    Leptin, acting as a measure of metabolic fuel availability, exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed (Hermann, G.E., Barnes, M.J., Rogers, R.C., 2006. Leptin and thyrotropin-releasing hormone: cooperative action in the hindbrain to activate brown adipose thermogenesis. Brain Res. 1117, 118-124.) a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain generated thermogenic responses. Specifically, exposure to both leptin and TRH elicited a 3.5 degrees C increase in brown adipose tissue [BAT] thermogenesis, while leptin alone did not evoke any change, and TRH alone caused only approximately 1 degrees C increase. The present study shows that the leptin-TRH synergy in controlling brown adipose [BAT] thermogenesis is order-specific and dependent on the feeding status of the animal. That is, fourth ventricular [4V] application of leptin to the food-deprived animal, before TRH injection, yields a substantial increase in BAT; while the reverse order yields a significantly smaller effect. If the animal were fed within minutes of anesthesia, then exogenous leptin was not necessary for TRH to yield a large increase in BAT temperature. The leptin-TRH synergy was uncoupled by pretreatment with the phosphoinositol-tris phosphate kinase [PI3K] inhibitor, wortmannin and the Src-SH2 antagonist, PP2. The TRH transduction mechanism utilizes phospholipase C [PLC] potently regulated by the SH2 site. Previous work in culture systems suggests that the product of PI3K activity [PIP3] potently upregulates PLC by activating the SH2 domain of the PLC complex. Perhaps leptin "gates" the thermogenic action of TRH in the hindbrain by invoking this same mechanism.

  8. 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.; 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

  9. Photoperiod-dependent regulation of gonadotropin-releasing hormone 1 messenger ribonucleic acid levels in the songbird brain

    OpenAIRE

    Stevenson, Authors: Tyler J; Bernard, Daniel J; McCarthy, Margaret M; Ball, Gregory F

    2013-01-01

    Annual changes in day length induce marked changes in reproductive function in temperate zone vertebrates. In many avian species, in contrast to other seasonally breeding animals, plasticity in hypothalamic gonadotropin-releasing hormone – 1 (GnRH1) expression rather than (or in addition to) release governs changes in pituitary-gonadal activity. Investigations of the cellular and molecular mechanisms that govern GnRH1 plasticity were previously hindered by a collective inability of scientists...

  10. Use of the Dexamethasone-Corticotrophin Releasing Hormone Test to Assess Hypothalamic-Pituitary-Adrenal Axis Function in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Eman A. Hasan

    2009-01-01

    Full Text Available Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA. A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L took dexamethasone (1.5 mg at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at −80∘C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P<.01. Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

  11. The role of Serine Proteases and Serine Protease Inhibitors in the migration of Gonadotropin-Releasing Hormone neurons

    Directory of Open Access Journals (Sweden)

    Silverman Ann-Judith

    2002-02-01

    Full Text Available Abstract Background Mechanisms regulating neuronal migration during development remain largely undefined. Extracellular matrix cues, target site released factors, and components of the migratory neurons themselves are likely all coordinated in time and space directing neurons to their appropriate locations. We have studied the effects of proteases and their inhibitors on the extracellular matrix and the consequences to the migration of gonadotropin releasing hormone (GnRH neurons in the embryonic chick. Chick GnRH neurons differentiate in the olfactory epithelium, migrate along the olfactory nerve and enter the forebrain. The accessibility of this coherent cell group make it amenable for studying protease/inhibitor roles in migratory processes. Results Affigel blue beads were used to deliver a serine protease inhibitor, protease nexin-1 (PN-1, and a target protease, trypsin, to the olfactory epithelium coincident with initiation of GnRH neuronal migration. PN-1 inhibited neuronal migration while trypsin accelerated their transit into the CNS. Prior to initiation of migration, neither PN-1 nor trypsin altered the timing of neuronal exit. Trypsin did, however, accelerate the timing of neuronal crossing into the nerve-forebrain junction. Conclusions These data support the hypothesis that protease activity modulates neuronal movements across barriers. Moreover, the data suggest, for the first time, that aspects of GnRH neuronal migration may be cell autonomous but modulated by ECM alterations.

  12. Characterization of a novel subtype of hippocampal interneurons that express corticotropin-releasing hormone.

    Science.gov (United States)

    Hooper, Andrew; Maguire, Jamie

    2016-01-01

    A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function. © 2015 Wiley Periodicals, Inc.

  13. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects.

    Science.gov (United States)

    Ma, Jing; Bellon, Max; Wishart, Judith M; Young, Richard; Blackshaw, L Ashley; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2009-04-01

    The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (approximately 290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (approximately 300 mosmol/l), all labeled with 150 mg 13C-acetate. Blood glucose increased only in response to sucrose (Psucralose or saline. Gastric emptying of sucrose was slower than that of saline (t50: 87.4+/-4.1 min vs. 74.7+/-3.2 min, Psucralose 0.4 mM (73.7+/-3.1 min) or 4 mM (76.7+/-3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans.

  14. Investigation of the effects of certain formulation factors on release ...

    African Journals Online (AJOL)

    Investigation of the effects of certain formulation factors on release properties of paracetamol tablets using 23 factorial design. ... The release properties of the tablets- measured by the disintegration and the dissolution times were used as assessment parameters. Results: Changing the concentration of factor A from” low” to ...

  15. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I

    Directory of Open Access Journals (Sweden)

    Alexander V. Sirotkin

    2016-02-01

    Full Text Available The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings and old (3-5 years of age minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml. We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a reduction in basal progesterone release and (b alterations in the response of estradiol but not of progesterone to leptin and IGF-I.

  16. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    Science.gov (United States)

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

  17. The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency

    DEFF Research Database (Denmark)

    Andersen, M; Støving, R K; Hangaard, J

    1998-01-01

    BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable such a...... nor by conventional HC therapy itself. However, our results also demonstrated that a GH-stimulation test should not be performed on patients, suffering from acute stress....... such as the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test. Three groups of subjects with a different GH-secretory capacity were included. STUDY A: Eight healthy adults were tested seven times, once with placebo throughout the examination and six times with the PD-GHRH test following no glucocorticoid......-responses to a PD-GHRH test were reduced in all individuals during acute stress-appropriate cortisol levels and the percentage reduction in GH-levels was independent of the GH-secretory capacity. Clinically, we found that peak GH-responses were not significantly affected by a short break in conventional HC therapy...

  18. Effects of various doses of ovine corticotrophin - releasing hormone on plasma and saliva cortisol concentrations in horses

    NARCIS (Netherlands)

    Reijerkerk, E.P.R.; Visser, E.K.; Reenen, van C.G.; Kolk, van der J.H.

    2009-01-01

    To compare the effects of IV administration of various doses of ovine corticotrophin¿releasing hormone (oCRH) on plasma and saliva cortisol concentrations in healthy horses and determine whether an oCRH challenge test protocol is valid for use in adult horses. Animals¿24 healthy Warmblood horses.

  19. Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms

    NARCIS (Netherlands)

    Wymenga, ANM; Eriksson, B; Salmela, PI; Jacobsen, MB; Van Cutsem, EJDG; Fiasse, RH; Valimaki, MJ; Renstrup, J; de Vries, EGE; Oberg, KE

    Purpose: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL), Patients and Methods:

  20. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD......) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor...... levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal...

  1. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    ) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor...... levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal....... This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...

  2. Somatostatin dramatically stimulates growth hormone release from primate somatotrophs acting at low doses via somatostatin receptor 5 and cyclic AMP.

    Science.gov (United States)

    Córdoba-Chacón, J; Gahete, M D; Culler, M D; Castaño, J P; Kineman, R D; Luque, R M

    2012-03-01

    Somatostatin and cortistatin have been shown to act directly on pituitary somatotrophs to inhibit growth hormone (GH) release. However, previous results from nonprimate species indicate that these peptides can also directly stimulate GH secretion, at low concentrations. The relevance of this phenomenon in a nonhuman primate model was investigated in the present study by testing the impact of somatostatin/cortistatin on GH release in primary pituitary cell cultures from baboons. High doses (> 10(-10) m) of somatostatin/cortistatin did not alter basal GH secretion but blocked GH-releasing hormone (GHRH)- and ghrelin-induced GH release. However, at low concentrations (10(-17)-10(-13) m), somatostatin/cortistatin dramatically stimulated GH release to levels comparable to those evoked by GHRH or ghrelin. Use of somatostatin receptor (sst) specific agonists/antagonists, and signal transduction blockers indicated that sst2 and sst1 activation via intact adenylate cylcase and mitogen-activated protein kinase systems mediated the inhibitory actions of high-concentration somatostatin. By contrast, the stimulatory actions of low-dose somatostatin on GH release were mediated by sst5 signalling through adenylate cylcase/cAMP/protein kinase A and intracellular Ca(2+) pathways, and were additive with ghrelin (not GHRH). Notably, low-concentrations of somatostatin, similar to sst5-agonists, inhibited prolactin release. These results clearly demonstrate that the ultimate impact of somatostatin/cortistatin on hormone release is dose-dependent, cell type-selective and receptor-specific, where the stimulatory effects of low-concentration somatostatin/cortistatin on GH release extend to primates, thereby supporting the notion that this action is relevant in regulating GH secretion in humans. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  3. Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

    Science.gov (United States)

    Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

    2012-01-01

    The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

  4. Effect of gonadotropin-releasing hormone and human chorionic gonadotropin on cows with ovarian follicular cysts.

    Science.gov (United States)

    Seguin, B E; Convey, E M; Oxender, W D

    1976-02-01

    Ovarian follicular cysts of cattle were defined as follicular structures (larger than or equal to 2.5 cm, diameter) which persisted for 10 days or longer in the absence of functional luteal tissue. Thirty dairy cows with ovarian follicular cysts were allotted to 6 groups (5 cows per group) and each was given 0 (saline solution), 25, 50, 100, 150, or 250 mug of gonadotropin-releasing hormone (GnRH) by intramuscular (IM) injection. Samples of blood were collected before GnRH was injected (0 hour), at 0.25, 0.50, 0.75, 1, 2, 3, and 4 hours, and at 1, 7, 11, 15, and 20 days after treatment. Five additional cows with follicular cysts were treated IM with 10,000 units of human chorionic gonadotropin (HCG), and blood sample collections were made before treatment (0 hour) and on days 1, 7, 11, 15, and 20 after treatment. Serum luteinizing hormone (LH) concentration was not altered in cows given saline solution, but was increased significantly in cows given any of the doses of GnRH (in a dose-related manner). Peak LH responses occurred about 2 hours after GnRH was given, and by 4 hours LH was beginning to decrease. Serum progesterone concentrations increased by more than 2.0 ng/ml by day 11 after treatment in 18 of 20 cows treated with 50, 100, 150, or 250 mug of GnRH. Progesterone responses in these cows were greater (P less than 0.05) than in cows given saline solution or a 25-mug dose of GnRH. Mean progesterone response to the 4 large doses of GnRH was similar in magnitude and duration to serum progesterone changes during the leutal phase of the bovine estrous cycle. After cows were treated with HCG, serum progesterone values were similar to those in cows given GnRH (50 to 250 mug).

  5. Influence of exogenous gonadotropin-releasing hormone on seasonal reproductive behavior of the coyote (Canis latrans).

    Science.gov (United States)

    Carlson, D A; Gese, E M

    2009-10-01

    Wild Canis species such as the coyote (C. latrans) express a suite of reproductive traits unusual among mammals, including perennial pair-bonds and paternal care of the young. Coyotes also are monestrous, and both sexes are fertile only in winter; thus, they depend upon social and physiologic synchrony for successful reproduction. To investigate the mutability of seasonal reproduction in coyotes, we attempted to evoke an out-of-season estrus in October using one of two short-acting gonadotropin-releasing hormone (GnRH) agents: (1) a GnRH analogue, deslorelin (6-D-tryptophan-9-(N-ethyl-L-prolinamide)-10-deglycinamide), 2.1mg pellet sc; or (2) gonadorelin, a GnRH (5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH(2)) porcine hypothalamic extract, 2.0 microg/kg im once daily for 3 consecutive days. A transient increase in serum concentrations of estradiol and progesterone (1 and 2 wk, respectively) was detected after treatment with deslorelin but not gonadorelin. Also, socio-sexual behaviors reminiscent of winter mating (including courtship, mate-guarding, precoital mounts, and copulatory ties) were observed among the deslorelin group. During the subsequent breeding season (January and February), however, preovulatory courtship behavior and olfactory sampling appeared suppressed; emergence of mounts and copulations were delayed in both deslorelin and gonadorelin treatment groups. Furthermore, whereas 8 of 12 females treated in October ovulated and produced healthy litters in the spring, 4 naïve coyotes failed to copulate or become pregnant. Thus, perturbation of hormones prior to ovulation in species with complex mating behaviors may disrupt critical intrapair relationships, even if fertility is not impaired physiologically.

  6. Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock.

    Science.gov (United States)

    Matejec, Reginald; Kayser, Friederike; Schmal, Frauke; Uhle, Florian; Bödeker, Rolf-Hasso; Maxeiner, Hagen; Kolbe, Julia Anna

    2013-09-01

    Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5μg/(kgbodyweighth) CRH (or placebo) were intravenously administered for 24h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, β-END immunoreacive material (IRM), β-LPH IRM, α-MSH and Nac-β-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16h after starting the CRH infusion; 8h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Invertebrate Gonadotropin-Releasing Hormone-Related Peptides and Their Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Tsubasa Sakai

    2017-09-01

    Full Text Available Gonadotropin-releasing hormones (GnRHs play pivotal roles in reproductive functions via the hypothalamus, pituitary, and gonad axis, namely, HPG axis in vertebrates. GnRHs and their receptors (GnRHRs are likely to be conserved in invertebrate deuterostomes and lophotrochozoans. All vertebrate and urochordate GnRHs are composed of 10 amino acids, whereas protostome, echinoderm, and amphioxus GnRH-like peptides are 11- or 12-residue peptide containing two amino acids after an N-terminal pyro-Glu. In urochordates, Halocynthia roretzi GnRH gene encodes two GnRH peptide sequences, whereas two GnRH genes encode three different GnRH peptides in Ciona intestinalis. These findings indicate the species-specific diversification of GnRHs. Intriguingly, the major signaling pathway for GnRHRs is intracellular Ca2+ mobilization in chordates, echinoderms, and protostomes, whereas Ciona GnRHRs (Ci-GnRHRs are endowed with multiple GnRHergic cAMP production pathways in a ligand-selective manner. Moreover, the ligand-specific modulation of signal transduction via heterodimerization among Ci-GnRHR paralogs suggests the species-specific development of fine-tuning of gonadal functions in ascidians. Echinoderm GnRH-like peptides show high sequence differences compared to those of protostome counterparts, leading to the difficulty in classification of peptides and receptors. These findings also show both the diversity and conservation of GnRH signaling systems in invertebrates. The lack of the HPG axis in invertebrates indicates that biological functions of GnRHs are not release of gonadotropins in current invertebrates and common ancestors of vertebrates and invertebrates. To date, authentic or putative GnRHRs have been characterized from various echinoderms and protostomes as well as chordates and the mRNAs have been found to be distributed not only reproductive organs but also other tissues. Collectively, these findings further support the notion that invertebrate Gn

  8. The pubertal spurt: effects of sex steroids on growth hormone and insulin-like growth factor I.

    Science.gov (United States)

    Caufriez, A

    1997-02-01

    In puberty, the growth spurt and the appearance of secondary sex characteristics occur concomitantly with an increase of sex steroids, growth hormone (GH) and insulin-like growth factor I (IGF-I). A number of experiments indicate that sex steroids exert a stimulatory action on the somatotropic axis. This effect is due to an amplifying action of oestradiol (secreted by the ovaries or after testosterone aromatization) on the neuroendocrine regulation of pulsatile GH release.

  9. 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.)

  10. Effect of priming injections of luteinizing hormone-releasing hormone on spermiation and ovulation in Gϋnther's Toadlet, Pseudophryne guentheri

    Directory of Open Access Journals (Sweden)

    Silla Aimee J

    2011-05-01

    Full Text Available Abstract Background In the majority of vertebrates, gametogenesis and gamete-release depend on the pulsatile secretion of luteinizing hormone-releasing hormone (LHRH from the hypothalamus. Studies attempting to artificially stimulate ovulation and spermiation may benefit from mimicking the naturally episodic secretion of LHRH by administering priming injections of a synthetic analogue (LHRHa. This study investigated the impact of low-dose priming injections of LHRHa on gamete-release in the Australian toadlet Pseudophryne guentheri. Methods Toadlets were administered a single dose of two micrograms per. gram LHRHa without a priming injection (no priming, or preceded by one (one priming or two (two priming injections of 0.4 micrograms per. gram LHRHa. Spermiation responses were evaluated at 3, 7 and 12 hrs post hormone administration (PA, and sperm number and viability were quantified using fluorescent microscopy. Oocyte yields were evaluated by stripping females at 10-11 hrs PA. A sub-sample of twenty eggs per female was then fertilised (with sperm obtained from testis macerates and fertilisation success determined. Results No priming induced the release of the highest number of spermatozoa, with a step-wise decrease in the number of spermatozoa released in the one and two priming treatments respectively. Peak sperm-release occurred at 12 hrs PA for all priming treatments and there was no significant difference in sperm viability. Females in the control treatment failed to release oocytes, while those administered an ovulatory dose without priming exhibited a poor ovulatory response. The remaining two priming treatments (one and two priming successfully induced 100% of females to expel an entire clutch. Oocytes obtained from the no, or two priming treatments all failed to fertilise, however oocytes obtained from the one priming treatment displayed an average fertilisation success of 97%. Conclusion Spermiation was most effectively induced in

  11. Biosynthesis and release of thyrotropin-releasing hormone immunoreactivity in rat pancreatic islets in organ culture. Effects of age, glucose, and streptozotocin

    DEFF Research Database (Denmark)

    Dolva, L O; Welinder, B S; Hanssen, K F

    1983-01-01

    chromatography and exhibited dilution curves parallel with synthetic TRH in radioimmunoassay. [3H]Histidine was incorporated into a component that reacted with TRH antiserum and had the same retention time as synthetic TRH on reversed-phase high-performance liquid chromatography. A continuous release of TRH......Thyrotropin-releasing hormone immunoreactivity (TRH-IR) was measured in isolated islets and in medium from rat pancreatic islets maintained in organ culture. TRH-IR in methanol extracts of both islets and culture medium was eluted in the same position as synthetic TRH by ion-exchange and gel...

  12. Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle.

    Science.gov (United States)

    Zhao, Hongqiong; Yannaing, Swe; Thanthan, Sint; Kuwayama, Hideto

    2011-11-01

    This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Regulation of hypothalamic corticotropin-releasing hormone neurone excitability by oxytocin.

    Science.gov (United States)

    Jamieson, B B; Nair, B B; Iremonger, K J

    2017-11-01

    Oxytocin (OT) is a neuropeptide that exerts multiple actions throughout the brain and periphery. Within the brain, OT regulates diverse neural populations, including neural networks controlling responses to stress. Local release of OT within the paraventricular nucleus (PVN) of the hypothalamus has been suggested to regulate stress responses by modulating the excitability of neighbouring corticotropin-releasing hormone (CRH) neurones. However, the mechanisms by which OT regulates CRH neurone excitability are unclear. In the present study, we investigated the morphological relationship between OT and CRH neurones and determined the effects of OT on CRH neurone excitability. Morphological analysis revealed that the processes of OT and CRH neurones were highly intermingled within the PVN, possibly allowing for local cell-to-cell cross-talk. Whole-cell patch-clamp recordings from CRH neurones were used to study the impact of OT on postsynaptic excitability and synaptic innervation. Bath-applied OT did not alter CRH neurone holding current, spiking output or any action potential parameters. Recordings of evoked excitatory and inhibitory postsynaptic currents (EPSCs/IPSCs) revealed no net effect of OT on current amplitude; however, subgroups of CRH neurones appeared to respond differentially to OT. Analysis of spontaneous EPSC events uncovered a significant reduction in spontaneous EPSC frequency but no change in spontaneous EPSC amplitude in response to OT. Together, these data demonstrate that OT exerts a subtle modulation of synaptic transmission onto CRH neurones providing one potential mechanism by which OT could suppress CRH neurone excitability and stress axis activity. © 2017 British Society for Neuroendocrinology.

  14. Dendro-dendritic bundling and shared synapses between gonadotropin-releasing hormone neurons

    Science.gov (United States)

    Campbell, Rebecca E.; Gaidamaka, Galina; Han, Seong-Kyu; Herbison, Allan E.

    2009-01-01

    The pulsatile release of gonadotropin-releasing hormone (GnRH) is critical for mammalian fertility, but the mechanisms underlying the synchronization of GnRH neurons are unknown. In the present study, the full extent of the GnRH neuron dendritic tree was visualized by patching and filling individual GnRH neurons with biocytin in acute brain slices from adult GnRH-green fluorescent protein (GFP) transgenic mice. Confocal analysis of 42 filled GnRH neurons from male and female adult mice revealed that the dendrites of the great majority of GnRH neurons (86%) formed multiple close appositions with dendrites of other GnRH neurons. Two types of interactions were encountered; the predominant interaction was one of vertical dendritic bundling where dendrites were found to wrap around each other in the same axis. The other interaction was one in which a GnRH neuron dendrite intercepted other GnRH neuron dendrites in a perpendicular fashion. Electron microscopy using pre-embedded, silver-enhanced immunogold labeling for both GnRH and GFP peptides in GnRH-GFP transgenic mice, confirmed that GnRH neuron dendrites were often immediately juxtaposed. Membrane specializations, including punctae and zonula adherens, were found connecting adjacent dendritic elements of GnRH neurons. Remarkably, individual afferent axon terminals were found to synapse with multiple GnRH neuron dendrites at sites of bundling. Together, these data demonstrate that GnRH neurons are not isolated from one another but, rather, interconnected via their long dendritic extensions. The observation of shared synaptic input to bundled GnRH neuron dendrites suggests a mechanism of GnRH neuron synchronization. PMID:19541658

  15. Molecular and functional characterization of a novel gonadotropin-releasing-hormone receptor isolated from the common octopus (Octopus vulgaris)

    Science.gov (United States)

    Kanda, Atsuhiro; Takahashi, Toshio; Satake, Honoo; Minakata, Hiroyuki

    2005-01-01

    GnRH (gonadotropin-releasing hormone) plays a pivotal role in the regulation of reproduction in vertebrates through interaction with a specific receptor. Previously, we isolated a GnRH homo-logue, oct-GnRH, from the common octopus (Octopus vulgaris). In the present study, we have identified a GnRH receptor (oct-GnRHR) specific for oct-GnRH from Octopus brain. Oct-GnRHR includes domains and motifs typical of vertebrate GnRH receptors. The intron-inserted positions are conserved between oct-GnRHR and the chordate GnRHR genes. The oct-GnRHR expressed in Xenopus (South African clawed frog) oocytes was responsive to oct-GnRH, but not to any other HPLC fractions of the Octopus brain extract. These results show that oct-GnRHR is an authentic receptor for oct-GnRH. Southern blotting of reverse-transcription PCR products revealed that the oct-GnRHR mRNA was widely distributed in the central and peripheral nervous systems and in several peripheral tissues. In situ hybridiz-ation showed that oct-GnRHR mRNA was expressed in some regions involved in autonomic functions, feeding, memory and movement. Oct-GnRH was shown to induce steroidogenesis of testosterone, progesterone and 17β-oestradiol in Octopus ovary and testis, where oct-GnRHR was abundantly expressed. These results suggest that oct-GnRH, like its vertebrate counterparts, acts as a multifunctional neurotransmitter, neuromodulator and hormone-like factor, both in Octopus central nervous system and peripheral tissues, and that both structure and functions of the GnRH family are, at least partially, evolutionarily conserved between octopuses and chordates. PMID:16367741

  16. Interaction of early life stress and corticotropin-releasing hormone receptor gene: effects on working memory.

    Science.gov (United States)

    Fuge, Philipp; Aust, Sabine; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Bajbouj, Malek; Grimm, Simone

    2014-12-01

    Early life stress (ELS) experience is associated with persisting working memory (WM) deficits; changes to the corticotropin-releasing hormone (CRH) system; and structural, functional, and epigenetic changes in the hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS experience to predict depression as well as neuroendocrine and neuronal reactivity. Although these findings indicate that vulnerable genotypes might also show impaired WM performance after ELS experience, no previous study investigated whether there is an interaction effect of CRHR1 polymorphisms and ELS experience on WM performance. Subjects (N = 451) were genotyped for rs110402 and rs242924 within the CRHR1 gene. We used an n-back task to investigate the hypothesis that WM performance in healthy subjects may be subtly influenced by functional differences in CRHR1 and represents an early marker of increased vulnerability after exposure to ELS. Exposure to ELS had a particularly strong impact on WM performance in subjects with the common homozygous GG GG genotype, whereas only severe exposure to ELS interfered with WM accuracy in AT carriers. Our data indicate that specific CRHR1 polymorphisms moderate the effect of ELS experience on WM performance. Exposure to ELS in combination with a vulnerable genotype results in subtle memory deficits in adulthood, which might develop before psychopathological symptoms. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Carina Lund

    2016-08-01

    Full Text Available Gonadotropin-releasing hormone (GnRH neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders.

  18. Presence and distribution of urocortin and corticotrophin-releasing hormone receptors in the bovine thyroid gland.

    Science.gov (United States)

    Squillacioti, C; De Luca, A; Alì, S; Ciarcia, R; Germano, G; Vittoria, A; Mirabella, N

    2014-12-01

    Urocortin (UCN), a 40 amino acid peptide, is a corticotrophin-releasing hormone (CRH)-related peptide. The biological actions of CRH family peptides are mediated via two types of G-protein-coupled receptors, CRH type 1 (CRHR1) and CRH type 2 (CRHR2). The aim of this study was to investigate the expression of UCN, CRHR1 and CRHR2 by immunoprecipitation, Western blot, immunohistochemistry and RT-PCR in the bovine thyroid gland. Immunoprecipitation and Western blot analysis showed that tissue extracts reacted with the anti-UCN, anti-CRHR1 and anti-CRHR2 antibodies. RT-PCR experiments demonstrated that mRNAs of UCN, CRHR1 and CRHR2 were expressed. UCN immunoreactivity (IR) and CRHR2-IR were found in the thyroid follicular and parafollicular cells and CRHR1-IR in the smooth muscle of the blood vessels. These results suggest that a regulatory system exists in the bovine thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through an autocrine/paracrine mechanism. © 2013 Blackwell Verlag GmbH.

  19. Expression of urocortin and corticotropin-releasing hormone receptors in the horse thyroid gland.

    Science.gov (United States)

    Squillacioti, Caterina; De Luca, Adriana; Alì, Sabrina; Paino, Salvatore; Liguori, Giovanna; Mirabella, Nicola

    2012-10-01

    Urocortin (UCN) is a 40-amino-acid peptide and a member of the corticotropin-releasing hormone (CRH) family, which includes CRH, urotensin I, sauvagine, UCN2 and UCN3. The biological actions of CRH family peptides are mediated via two types of G-protein-coupled receptors, namely CRH type 1 receptor (CRHR1) and CRH type 2 receptor (CRHR2). The biological effects of these peptides are mediated and modulated not only by CRH receptors but also via a highly conserved CRH-binding protein (CRHBP). Our aim was to investigate the expression of UCN, CRHR1, CRHR2 and CRHBP by immunohistochemistry, Western blot and reverse transcription with the polymerase chain reaction (RT-PCR) in the horse thyroid gland. The results showed that UCN, CRHR1 and CRHR2 were expressed in the thyroid gland, whereas CRHBP was not expressed. Specifically, UCN immunoreactivity (-IR) was found in the thyroid follicular cells, CRHR2-IR in the C-cells and CRHR1-IR in blood vessels. Western blot analysis and RT-PCR experiments confirmed the immunohistochemical data. These results suggest that a regulatory system exists in the mammalian thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through a paracrine mechanism.

  20. Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

    Science.gov (United States)

    Rosati, Fabiana; Sturli, Niccolò; Cungi, Maria Chiara; Morello, Matteo; Villanelli, Fabio; Bartolucci, Gianluca; Finocchi, Claudia; Peri, Alessandro; Serio, Mario; Danza, Giovanna

    2011-04-01

    Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.0 nM. The expression of Hydroxysterol D24-reductase (seladin-1/DHCR24), that catalyzes the last step of cholesterol biosynthesis, is increased by 50% after 90 min of incubation with GnRH. StAR protein and P450 side chain cleavage (P450scc) are up-regulated by 3.3 times after 90 min and by 3.5 times after 3 h, respectively. GnRH action is mediated by LH and 1.0 nM GnRH enhances the expression of LHβ as well. A two fold increase of cell cholesterol is induced after 90 min of GnRH incubation and 17β-estradiol (E2) production is increased after 24, 48 and 72 h. These data indicate for the first time that GnRH regulates both cholesterol and steroid biosynthesis in human neuronal-like cells and suggest a new physiological role for GnRH in the brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Influence of thyrotropin-releasing hormone (TRH) dialyzed into the hippocampus on memory processes in rabbit.

    Science.gov (United States)

    Orlowska-Majdak, Monika; Naziemblo, Barbara; Kolodziejski, Pawel

    2007-01-01

    There are conflicting reports on the influence of thyrotropin-releasing hormone (TRH) on the process of learning. We decided to study this problem using the paradigm of classical eyeblink conditioning as the animal model of learning processes. During the extinction training TRH in its natural form of pG1uTRH was applied into the rabbit hippocampus through a chronically implanted microdialysis probe. A Glu(1)TRH, analog with less biological potency than TRH as the control of specificity for TRH and a 0.9% NaCl solution as the control for both substances were applied by the same way as pGluTRH. We found that pGluTRH extended the process of extinction and enhanced the further acquisition of the reflex. The analog of TRH, Glu(1)TRH, was ineffective. Finally, it may be stated that TRH acting in the hippocampus prolonged process of forgetting and improved succeeding learning. The effect was specific and long lasting.

  2. Thyrotropin-releasing hormone (TRH promotes wound re-epithelialisation in frog and human skin.

    Directory of Open Access Journals (Sweden)

    Natalia T Meier

    Full Text Available There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression. Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

  3. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  4. Tolerability of the dexamethasone-corticotropin releasing hormone test in major depressive disorder.

    Science.gov (United States)

    Dunlop, Boadie W; Betancourt, Yara; Binder, Elisabeth B; Heim, Christine; Holsboer, Florian; Ising, Marcus; McKenzie, Melissa; Mletzko, Tanja; Pfister, Hildegard; Nemeroff, Charles B; Craighead, W Edward; Mayberg, Helen S

    2011-01-01

    The dexamethasone-corticotropin releasing hormone (Dex-CRH) test may differentially predict which depressed patients will respond to antidepressant medication. However, a comprehensive analysis of the safety of this test in psychiatric patients has not previously been performed. We conducted a pooled analysis of depressed patients in four clinical studies. Observed and subjectively reported side-effects in 454 patients were collected for 90 minutes following CRH administration. Pre-test electrocardiograms were available in 250 patients to assess cardiac safety. Descriptive statistics were performed to evaluate these safety data. Eight-six (18.9%) subjects experienced no side-effects from the procedure. The mean number of side-effects per subject was 1.4±1.0. The most frequent adverse events were: flushing (n=216, 47.6%), feeling of warmth (144, 31.7%), hyperpnea/tachypnea (108, 23.8%), palpitations (37, 8.1%), and tachycardia (28, 6.2%). Side-effects were consistently mild and brief in duration. There were no serious adverse events. The Dex-CRH test produces a mild, predictable side-effect profile, characterized by flushing, feelings of warmth, hyperpnea/tachypnea, palpitations, and tachycardia. These results provide reassurance that the Dex-CRH test is well tolerated in psychiatric patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Development of a radioimmunoassay for measuring gonadotrophin releasing hormone in patients receiving treatment

    Energy Technology Data Exchange (ETDEWEB)

    Mobsby, V.A.; Knapp, M.L.; Mayne, P.D. (Charing Cross and Westminster Medical School, Westminster, London (UK)); Fink, R.S. (West Middlesex Univ. Hospital, Isleworth (UK)); Osgood, V.M. (Royal Free Hospital, London (UK))

    1989-05-01

    This gonadotrophin releasing hormone (GnRH) assay showed good precision, recovery, and parallelism over a wide range of GnRH concentrations with a sensitivity of 15 pg/ml. The assay was compared with a commercially available kit (Buhlmann Laboratories). Although the Buhlmann kit showed acceptable precision, recovery, sensitivity, and correlation with the developed GnRH assay for plasma samples, lack of parallelism of serially diluted plasma and urine samples was consistently observed, together with poor correlation with the developed GnRH assay for urine, suggesting a matrix effect with the Buhlmann kit. The developed assay is suitable for measuring GnRH in samples obtained from patients receiving pulsatile infusions of GnRH. In contrast, the commercially available Buhlmann kit was unsuitable for measuring plasma GnRH as the kit had a top standard of only 160 pg/ml, well below peak plasma concentration. It would not be possible to dilute samples for analysis because of lack of parallelism of diluted samples compared with standards obtained with the Buhlmann assay. (author).

  6. Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men.

    Science.gov (United States)

    Austin, M C; Janosky, J E; Murphy, H A

    2003-03-01

    A number of clinical investigations and postmortem brain studies have provided evidence that excessive corticotropin-releasing hormone (CRH) secretion and neurotransmission is involved in the pathophysiology of depressive illness, and several studies have suggested that the hyperactivity in CRH neurotransmission extends beyond the hypothalamus involving several extra-hypothalamic brain regions. The present study was designed to test the hypothesis that CRH levels are increased in specific brainstem regions of suicide victims with a diagnosis of major depression. Frozen tissue sections of the pons containing the locus coeruleus and caudal raphe nuclei from 11 matched pairs of depressed suicide and control male subjects were processed for radioimmunocytochemistry using a primary antiserum to CRH and a ([125])I-IgG secondary antibody. The optical density corresponding to the level of CRH-immunoreactivity (IR) was quantified in specific pontine regions from the film autoradiographic images. The level of CRH-IR was increased by 30% in the locus coeruleus, 39% in the median raphe and 45% in the caudal dorsal raphe in the depressed suicide subjects compared to controls. No difference in CRH-IR was found in the dorsal tegmentum or medial parabrachial nucleus between the subject groups. These findings reveal that CRH-IR levels are specifically increased in norepinephrine- and serotonin-containing pontine nuclei of depressed suicide men, and thus they are consistent with the hypothesis that CRH neurotransmission is elevated in extra-hypothalamic brain regions of depressed subjects.

  7. 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.

  8. Corticotropin-releasing hormone receptor-1 and histidine decarboxylase expression in chronic urticaria.

    Science.gov (United States)

    Papadopoulou, Nikoletta; Kalogeromitros, Demetrios; Staurianeas, Nikolaos G; Tiblalexi, Despina; Theoharides, Theoharis C

    2005-11-01

    Certain skin disorders, such as contact dermatitis and chronic urticaria, are characterized by inflammation involving mast cells and worsen by stress. The underlying mechanism of this effect, however, is not known. The skin appears to have the equivalent of a hypothalamic-pituitary-adrenal (HPA) axis, including local expression of corticotropin-releasing hormone (CRH) and its receptors (CRH-R). We have reported that acute stress and intradermal administration of CRH stimulate skin mast cells and increase vascular permeability through CRH-R1 activation. In this study, we investigated the expression of CRH-R1, the main CRH-R subtype in human skin, and the mast cell related gene histidine decarboxylase (HDC), which regulates the production of histamine, in normal and pathological skin biopsies. Quantitative real time PCR revealed that chronic urticaria expresses high levels of CRH-R1 and HDC as compared to normal foreskin, breast skin and cultured human keratinocytes. The lichen simplex samples had high expression of CRH-R1, but low HDC. These results implicate CRH-R in chronic urticaria, which is often exacerbated by stress.

  9. Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin.

    Science.gov (United States)

    Meier, Natalia T; Haslam, Iain S; Pattwell, David M; Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E; Hardman, Matthew J; Paus, Ralf

    2013-01-01

    There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

  10. Development of a radioimmunoassay for measuring gonadotrophin releasing hormone in patients receiving treatment.

    Science.gov (United States)

    Mosby, V A; Knapp, M L; Fink, R S; Osgood, V M; Mayne, P D

    1989-05-01

    A radioimmunoassay for the measurement of gonadotrophin releasing hormone (GnRH) in plasma and urine using readily available reagents was developed. The GnRH assay showed good precision, recovery, and parallelism over a wide range of GnRH concentrations with a sensitivity of 15 pg/ml. The assay was compared with a commercially available kit (Buhlmann Laboratories). Although the Buhlmann kit showed acceptable precision, recovery, sensitivity, and correlation with the developed GnRH assay for plasma samples, lack of parallelism of serially diluted plasma and urine samples was consistently observed, together with a poor correlation with the developed GnRH assay for urine, suggesting a matrix effect with the Buhlmann kit. The developed assay is suitable for measuring GnRH in samples obtained from patients receiving pulsatile infusions of GnRH. In contrast, the commercially available Buhlmann kit was unsuitable for measuring plasma GnRH as the kit had a top standard of only 160 pg/ml, well below the peak plasma concentration. It would not be possible to dilute samples for analysis because of the lack of parallelism of diluted samples compared with standards obtained with the Buhlmann assay.

  11. Gonadotropin-releasing hormone targeting for gonadotroph ablation: an approach to non-surgical sterilization.

    Science.gov (United States)

    Struthers, R S

    2012-08-01

    Surgical sterilization is the mainstay of dog and cat population control, but its use is still often limited by the costs and effort involved, especially in developing countries. An ideal non-surgical sterilant that is safe, effective, permanent, administered as a single injection and capable of being manufactured inexpensively could have a significant impact on the world-wide dog and cat overpopulation problem. One approach towards developing such an agent is the targeting of pituitary gonadotrophic cells with cytotoxic agents using gonadotropin-releasing hormone (GnRH). GnRH is a peptide that binds to high-affinity receptors selectively expressed on gonadotrophs and some types of cancers. Both small molecules and proteins have been conjugated to GnRH analogues to generate targeted cytotoxic and imaging agents. Although most of these efforts have focused on development of human cancer therapeutics, available reproductive studies in rats and dogs suggest that current compounds do not have sufficient therapeutic windows for complete gonadotroph ablation, in part owing to poor stability of peptide targeting sequences. The only reported longer-term study of gonadotroph ablation in dogs reported suppression of serum testosterone for 8 months, but endocrine function then recovered, raising important questions about the mechanism of reproductive suppression and its recovery. Although studies to date suggest that this is a potentially attractive approach to non-surgical sterilization, ideal agents are yet to be developed, and important mechanistic questions remain to be answered. © 2012 Blackwell Verlag GmbH.

  12. The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

    Science.gov (United States)

    Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

    2017-06-30

    Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Interaction between salsolinol (SAL) and thyrotropin-releasing hormone (TRH) or dopamine (DA) on the secretion of prolactin in ruminants.

    Science.gov (United States)

    Hashizume, T; Shida, R; Suzuki, S; Kasuya, E; Kuwayama, H; Suzuki, H; Oláh, M; Nagy, G M

    2008-04-01

    We have recently demonstrated that salsolinol (SAL), a dopamine (DA)-derived compound, is present in the posterior pituitary gland and is able to stimulate the release of prolactin (PRL) in ruminants. The aim of the present study was to clarify the effect that the interaction of SAL with thyrotropin-releasing hormone (TRH) or DA has on the secretion of PRL in ruminants. A single intravenous (i.v.) injection of SAL (5mg/kg body weight (b.w.)), TRH (1microg/kg b.w.), and SAL plus TRH significantly stimulated the release of PRL in goats (PTRH than either SAL or TRH alone, respectively (PTRH (1microg/kg b.w.) significantly stimulated the release of PRL in goats (PTRH than either sulpiride alone or sulpiride plus SAL, respectively (PTRH (10(-8)M), and SAL plus TRH significantly increased the release of PRL (PTRH detected in vivo was not observed in vitro. In contrast, DA (10(-6)M) inhibited the TRH-, as well as SAL-induced PRL release in vitro. All together, these results clearly show that SAL can stimulate the release of PRL in ruminants. Furthermore, they also demonstrate that the additive effect of SAL and TRH on the release of PRL detected in vivo may not be mediated at the level of the AP, but that DA can overcome their releasing activity both in vivo and in vitro, confirming the dominant role of DA in the inhibitory regulation of PRL secretion in ruminants.

  14. Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: evidence for a pituitary site of action.

    Science.gov (United States)

    Barb, C R; Hausman, G J

    2009-06-01

    Three experiments (EXP) were conducted to determine the role of insulin-like growth factor-I (IGF-I) in the control of growth hormone (GH) and LH secretion. In EXP I, prepuberal gilts, 65 ± 6 kg body weight and 140 days of age received intracerebroventricular (ICV) injections of saline (n = 4), 25 μg (n = 4) or 75 μg (n = 4) IGF-I and jugular blood samples were collected. In EXP II, anterior pituitary cells in culture collected from 150-day-old prepuberal gilts (n = 6) were challenged with 0.1, 10 or 1000 nM [Ala15]-h growth hormone-releasing hormone-(1-29)NH2 (GHRH), or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 1000 nM GHRH. Secreted GH was measured at 4 and 24 h after treatment. In EXP III, anterior pituitary cells in culture collected from 150-day-old barrows (n = 5) were challenged with 10, 100 or 1000 nM gonadotropin-releasing hormone (GnRH) or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 100 nM GnRH. Secreted LH was measured at 4 h after treatment. In EXP I, serum GH and LH concentrations were unaffected by ICV IGF-I treatment. In EXP II, relative to control all doses of GHRH increased (P 0.1). In conclusion, under these experimental conditions the results suggest that the pituitary is the putative site for IGF-I modulation of GH and LH secretion. Further examination of the role of IGF-I on GH and LH secretion is needed to understand the inhibitory and stimulatory action of IGF-I on GH and LH secretion.

  15. Identification of a gonadotropin-releasing hormone receptor orthologue in Caenorhabditis elegans

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    Sgro Jean-Yves

    2006-11-01

    Full Text Available Abstract Background The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs, but the GPCR(s critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR exist in C. elegans. Results Our sequence analyses indicated the presence of two proteins in C. elegans, one of 401 amino acids [GenBank: NP_491453; WormBase: F54D7.3] and another of 379 amino acids [GenBank: NP_506566; WormBase: C15H11.2] with 46.9% and 44.7% nucleotide similarity to human GnRHR1 and GnRHR2, respectively. Like human GnRHR1, structural analysis of the C. elegans GnRHR1 orthologue (Ce-GnRHR predicted a rhodopsin family member with 7 transmembrane domains, G protein coupling sites and phosphorylation sites for protein kinase C. Of the functionally important amino acids in human GnRHR1, 56% were conserved in the C. elegans orthologue. Ce-GnRHR was actively transcribed in adult worms and immunoanalyses using antibodies generated against both human and C. elegans GnRHR indicated the presence of a 46-kDa protein, the calculated molecular mass of the immature Ce-GnRHR. Ce-GnRHR staining was specifically localized to the germline, intestine and pharynx. In the germline and intestine, Ce-GnRHR was localized specifically to nuclei as revealed by colocalization with a DNA nuclear stain. However in the pharynx, Ce-GnRHR was localized to the myofilament lattice of the pharyngeal musculature, suggesting a functional role for Ce-GnRHR signaling in the coupling of food intake with reproduction. Phylogenetic analyses support an early evolutionary origin of GnRH-like receptors, as evidenced by the hypothesized grouping of Ce-GnRHR, vertebrate GnRHRs, a molluscan GnRHR, and the adipokinetic hormone receptors (AKHRs and corazonin receptors of arthropods. Conclusion This is the first report of a GnRHR orthologue in C. elegans, which

  16. Mental illness, criminal risk factors and parole release decisions.

    Science.gov (United States)

    Matejkowski, Jason; Draine, Jeffrey; Solomon, Phyllis; Salzer, Mark S

    2011-01-01

    Research has not examined whether higher rates of parole denial among inmates with mental illness (MI) are the result of the increased presence of criminal risk factors among this population. Employing a representative sample of inmates with (n  =  219) and without (n  =  184) MI receiving parole release decisions in 2007, this study tested whether the central eight risk factors for recidivism considered in parole release decisions intervened in the relationship between MI and parole release. MI was associated with possession of a substance use disorder, antisocial personality disorder and violent charges while incarcerated; however, these factors were not related to release decisions. MI was found to have neither a direct nor an indirect effect on release decisions. While results indicate that release decisions appear, to some extent, to be evidence-based, they also suggest considerable discretion is being implemented by parole board members in release decisions above and beyond consideration of criminal risk factors. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience.

    Science.gov (United States)

    Zhou, Fan; Zhang, Li; He, Mao Mao; Liu, Zheng Fei; Gao, Bing Xin; Wang, Xiao Dong

    2014-08-01

    Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP). One hundred pregnant women diagnosed with ICP at 34-34(+6) weeks of gestation agreed to participate in this prospective nested case-control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues. The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in different gestational weeks and TBA levels to provide more evidence for the correlation between UDCA treatment and CRH expression in ICP patients.

  18. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Energy Technology Data Exchange (ETDEWEB)

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  19. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

    Science.gov (United States)

    Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

    2003-09-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

  20. Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries.

    Science.gov (United States)

    Minoves, Nuria; Balfagón, Gloria; Ferrer, Mercedes

    2002-09-01

    This study examines the effects of female sex hormones on the vasoconstrictor response to electrical field stimulation (EFS), as well as the modulation of this response by neuronal NO. For this purpose, segments of denuded superior mesenteric artery from ovariectomized (OvX) female Sprague-Dawley rats and from control rats (in oestrus phase) were used. EFS induced frequency-dependent contractions, which were greater in segments from OvX rats than in those from control rats. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester strengthened EFS-elicited contractions to a greater extent in arteries from OvX rats than in those from control rats. Similar results were observed with the preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial neurotoxin capsaicin did not modify EFS-induced contractions in segments from either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP) induced concentration-dependent relaxation, which was greater in segments from control rats than in those from OvX rats. 8-Bromo-cGMP induced similar concentration-dependent relaxation in noradrenaline-precontracted segments from both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD) inhibitor, reduced the relaxation induced by SNP in segments from both groups of rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP in segments from OvX rats, but did not modify it in segments from control rats. EFS induced NO(-)(2) formation, which was greater in segments from OvX than in those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve impulse propagation, abolished release in both cases. These results suggest that EFS induces greater neuronal NO release in mesenteric segments from OvX rats than in those from control rats and, although NO metabolism is also higher, the contribution of net neuronal NO in the vasomotor response to EFS is greater in segments from OvX rats than in those

  1. Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.

    Science.gov (United States)

    Lu, Jie; Montgomery, Blake K; Chatain, Grégoire P; Bugarini, Alejandro; Zhang, Qi; Wang, Xiang; Edwards, Nancy A; Ray-Chaudhury, Abhik; Merrill, Marsha J; Lonser, Russell R; Chittiboina, Prashant

    2017-10-03

    Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18 F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18 F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas. Clinical data was analyzed for efficacy of CRH in improving 18 FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells. CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p fasentin suppressed baseline (p < 0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation. Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18 F-FDG PET could improve microadenoma detection. Copyright © 2017. Published by Elsevier B.V.

  2. Inhibition of thyrotropin response to TSH-releasing hormone by thyroxine in hypothyroid rats

    Energy Technology Data Exchange (ETDEWEB)

    Boado, R.J.; Zaninovich, A.A.; Ulloa, E.R.; Fernandez Pol, J.A.

    1985-05-01

    Pharmacological amounts of throxine (T4) can inhibit the thyrotropin (TSH) response to TSH-releasing hormone (TRH) before its conversion to triiodothyronine (T3) in the hypophysis of euthyroid rate. The present work tested physiological doses of T4 in hypothyroid rats. Rats were treated with iopanoic acid (IOP) 5 mg/100 g BW 24, 12 and 1.5 hours preceding the study, to prevent intrapituitary conversion of T4 to T3. Nonradioactive T4 was injected iv at time 0. At 20 min a 1 ..mu..g/100 g BW dose of TRH was injected iv. Blood samples were drawn at times 0, 20, and 30 min for determination by radioimmunoassay of plasma T4, T3, and TSH. In untreated rats basal TSH was 1450 +- 200 (SEM) ..mu..U/ml. At 20 min it was 105 +- 12% the basal value and at 30 min (10 min post-TRH) plasma TSH rose to 165 +- 14%. In T4-treated rats, those injected with IOP or with the vehicle alone both had the TSH response suppressed. IOP reduced intrapitutiary T3 from 4.6 +- 2.4 to 0.5 +- 0.2 fmol/min/gland. Thirty min. following the iv injection of 150 ..mu..Ci of double-labeled /sup 125/I-T4, the in vitro cytoplasmic radioactivity in control rats was 1.3 +- 0.13 x 10-/sup 2/% of the injected dose (75% T4, 17% T3), while in nuclei it was 4.2 +- 3.6 x 10-/sup 3/% (5l% T4, 28% T3). The injection of 25 ..mu..g of nonradioactive T4 decreased /sup 125/I-T4 in cytoplasm with no changes in nuclei. These findings suggest an intrinsic capacity of T4 to control TRH stimulation of TSH through binding to cytoplasmic receptors.

  3. Gonadotropin releasing hormone in the primitive vertebrate family Myxinidae: reproductive neuroanatomy and evolutionary aspects.

    Science.gov (United States)

    Sills, Eric Scott; Palermo, Gianpiero D

    2013-01-01

    The family Myxinidae embraces all hagfish species, and occupies an evolutionary niche intermediate between ancestral vertebrates and the gnathostomes (jawed vertebrates). Gonadotropin releasing hormone (GnRH) modulates neuroendocrine activity in vertebrates and works in the context of the hypothalamic-pituitary (H-P) axis. The appearance of this neuroendocrine axis marks one of the most crucial developmental achievements in vertebrate evolution, because it enabled further diversification in general growth, metabolism, osmoregulation and reproduction as jawed vertebrates evolved. GnRH studies in hagfish draw attention because such work may be considered as providing proxy data for similar investigations conducted upon long extinct species. Indeed, the fossil record reveals little anatomical difference between those hagfish living 300 million years ago and their modern descendants. Accordingly, the hagfish can offer important evolutionary lessons as they have some highly unusual characteristics not seen in any other vertebrate; they retain many representative features of an ancestral state from which all vertebrates originated. Indeed, because central control of reproduction is perhaps the most basic function of the vertebrate H-P axis, and given the importance of GnRH in this network, research on GnRH in hagfish can help elucidate the early evolution of the H-P system itself. Like all vertebrates, hagfish have a functional hypothalamic area and a pituitary gland, constituting a basic H-P axis. But what role does GnRH play in the reproductive system of this "living fossil"? How can understanding GnRH in hagfish help advance the knowledge of vertebrate neuroendocrinology? Here, information on neuroendocrine function and the role of GnRH specifically in this very basal vertebrate is reviewed.

  4. Activity-dependent modulation of gonadotrophin-releasing hormone neurone activity by acute oestradiol.

    Science.gov (United States)

    Romanò, Nicola; Herbison, Allan E

    2012-10-01

    Oestradiol (E₂) exerts potent feedback actions upon gonadotrophin-releasing hormone (GnRH) neurones and part of this feedback action may occur through the rapid action of E₂. Using a transgenic GnRH-Pericam mouse line that allows real-time intracellular calcium concentrations ([Ca²⁺](i)) to be monitored in adult GnRH neurones in a brain slice preparation, we examined the acute effects of 100 pM-100 nM E₂ on [Ca²⁺](i) transients in spontaneously active GnRH neurones. Approximately 30% of GnRH neurones exhibit spontaneous [Ca²⁺](i) transients at a frequency greater than two transients/15 min in adult female mice. In these cells, treatment with an incremental 1, 10, 100 nM E₂ protocol or 100 pM E₂ alone resulted in the suppression or complete cessation of [Ca²⁺](i) transients in 15 of 18 (83%) GnRH neurones. This effect was mimicked by E₂ bound to albumin, suggesting a membrane site of action, and was maintained in oestrogen receptor β knockout mice, indicating that this receptor is not essential for the rapid suppression of [Ca²⁺](i) transients. These findings contrast with those GnRH neurones exhibiting very few or no [Ca²⁺](i) transients (neurone burst firing and that E₂ suppression or activation of [Ca²⁺](i) transients was mirrored by a depression or initiation of burst firing. Taken together, these studies demonstrate that the acute actions of E₂ on GnRH neurones are critically dependent upon their pattern of burst firing. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

  5. Preserving fertility when choosing chemotherapy regimens - the role of gonadotropin-releasing hormone agonists.

    Science.gov (United States)

    Blumenfeld, Zeev; Evron, Ayelet

    2015-05-01

    The late effects of cancer treatment have recently gained a worldwide ubiquitous interest among reproductive endocrinologists, oncologists, and all health care providers. Despite many publications on this subject, there are many equivocal issues necessitating summary. The case for and against using GnRH-agonist for fertility preservation is summarized with the rationale that preventing ovarian failure may be better than treating it. We searched Medline in the last 10 years using terms: 'fertility preservation', 'female chemotherapy', 'Gonadotropin-releasing hormone (GnRH) analogues', 'GnRH agonists' 'gonadotoxicity', and 'cancer treatment'. We included mainly publications from the past 7 years, but did not exclude previous, commonly referenced publications. Here, we summarize the various methods available for fertility preservation and minimizing chemotherapy induced gonadotoxicity. Until now, 20 studies (15 retrospective and 5 randomized controlled trial) have reported on 2038 patients treated with GnRH-a in parallel to chemotherapy, showing a significant decrease in premature ovarian failure (POF) rate in survivors versus 8 studies reporting on 509 patients, with negative results. Patients treated with GnRH-a in parallel to chemotherapy preserved their cyclic ovarian function in 91% of cases as compared to 41% of controls, with a pregnancy rate of 19 - 71% in the treated patients. Furthermore, over 10 recent meta-analyses have concluded that GnRH-a are beneficial and may decrease the risk of POF in survivors. Because most of the methods involving ovarian or egg cryopreservation are not yet clinically established and unequivocally successful, these young patients deserve to be informed with all the various modalities to minimize gonadal damage and preserve ovarian function and future fertility. Combining the various modalities for a specific patient may increase the odds of preservation of future fertility.

  6. Thyrotropin-Releasing Hormone-Containing Axons Innervate Histaminergic Neurons in the Tuberomammillary Nucleus

    Science.gov (United States)

    Sárvári, Anna; Farkas, Erzsébet; Kádár, Andrea; Zséli, Györgyi; Füzesi, Tamás; Lechan, Ronald M.; Fekete, Csaba

    2012-01-01

    Recent studies indicate that the effect of thyrotropin-releasing hormone (TRH) on the regulation of food intake may be mediated by histaminergic neurons. To elucidate the anatomical basis for a functional relationship between TRH- and histamine-synthesizing neuronal systems, double-labeling immunocytochemistry was performed on the tuberomammillary nucleus (TMN) of rats, the exclusive location of histaminergic neurons. TRH-immunoreactive (IR) innervation of the histaminergic neurons were detected in all five subnuclei (E1-5) of the TMN, but was most prominent in the E4 and E5 subnuclei where 100% of the histamine-IR neurons were contacted. The number of TRH-IR varicosities in contact with histamine-IR neurons was also greatest in the E4 and E5 subnuclei, averaging 27.0±1.2 in E4 and 7.9±0.5 in E5. Somewhat fewer histamine-IR neurons were juxtaposed by TRH-IR varicosities in E2 and E3 and contacted by 6.3 ± 0.2 and 6.8 ± 0.2 varicosities/innervated cell, respectively. The number of juxtapositions of TRH-IR axon varicosities with histamine-IR neurons was the lowest in the E1 subnucleus (85.7±0.9%; 4.0±0.2 varicosities/innervated cell). Ultrastructural analysis demonstrated that TRH-IR axons established both asymmetric and symmetric type synapses on the perikaryon and dendrites of the histamine-IR neurons, although the majority of synapses were asymmetric type. These data demonstrate that TRH neurons heavily innervate histaminergic neurons in all subdivisions of the TMN, with the densest innervation in the E4 and E5 subdivisions, and are likely to exert activating effects. PMID:23063458

  7. INVESTIGATIONS INTO THE MECHANISM OF REDUCTION OF ETHANOL SLEEP BY THYROTROPIN - RELEASING HORMONE (TRH)1

    Science.gov (United States)

    COTT, JERRY M.; BREESE, GEORGE R.; COOPER, BARRETT R.; BARLOW, T. STEVEN; PRANGE, ARTHUR J.

    2010-01-01

    Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content. This reduction of the actions of ethanol was also apparent after oral or intracisternal administration of TRH. In addition, TRH reduced ethanol-induced sleep in rats, hamsters, gerbils and guinea pigs. Evidence that the pituitary-thyroid axis is not necessary for the effects of TRH was provided by observations that hypophysectomy did not reduce TRH antagonism of ethanol narcosis and findings that neither triiodothyronine nor thyrotropin mimicked its action. Certain analogs of TRH, which have little effect on the pituitary, were also found to antagonize ethanol-induced sleep and hypothermia. Pretreatment with the antiadrenergic drugs, α-methyltyrosine, phentolamine and propranolol did pot antagonize the ability of TRH to reduce sleep induced by ethanol. However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent. In contrast, central administration of other anticholinergic drugs, such as d-tubocurarine and hexamethonium, reduced ethanol-induced sleep and this effect was additive with TRH. Carbachol also reduced ethanol sleeping time and this effect was also blocked by atropine methyl nitrate. The antagonism of ethanol-induced sleep by dibutyryl cyclic adenosine 3′,5′-monophosphate was significantly reduced but not blocked by atropine methyl nitrate. Results provide evidence that TRH has a direct extrapituitary action on brain and that both TRH and ethanol may interact with central cholinergic systems. PMID:177753

  8. Desensitization, Trafficking, and Resensitization of the Pituitary Thyrotropin-Releasing Hormone Receptor

    Science.gov (United States)

    Hinkle, Patricia M.; Gehret, Austin U.; Jones, Brian W.

    2012-01-01

    The pituitary receptor for thyrotropin-releasing hormone (TRH) is a calcium-mobilizing G protein-coupled receptor (GPCR) that signals through Gq/11, elevating calcium, and activating protein kinase C. TRH receptor signaling is quickly desensitized as a consequence of receptor phosphorylation, arrestin binding, and internalization. Following activation, TRH receptors are phosphorylated at multiple Ser/Thr residues in the cytoplasmic tail. Phosphorylation catalyzed by GPCR kinase 2 (GRK2) takes place rapidly, reaching a maximum within seconds. Arrestins bind to two phosphorylated regions, but only arrestin bound to the proximal region causes desensitization and internalization. Phosphorylation at Thr365 is critical for these responses. TRH receptors internalize in clathrin-coated vesicles with bound arrestin. Following endocytosis, vesicles containing phosphorylated TRH receptors soon merge with rab5-positive vesicles. Over approximately 20 min these form larger endosomes rich in rab4 and rab5, early sorting endosomes. After TRH is removed from the medium, dephosphorylated receptors start to accumulate in rab4-positive, rab5-negative recycling endosomes. The mechanisms responsible for sorting dephosphorylated receptors to recycling endosomes are unknown. TRH receptors from internal pools help repopulate the plasma membrane. Dephosphorylation of TRH receptors begins when TRH is removed from the medium regardless of receptor localization, although dephosphorylation is fastest when the receptor is on the plasma membrane. Protein phosphatase 1 is involved in dephosphorylation but the details of how the enzyme is targeted to the receptor remain obscure. It is likely that future studies will identify biased ligands for the TRH receptor, novel arrestin-dependent signaling pathways, mechanisms responsible for targeting kinases and phosphatases to the receptor, and principles governing receptor trafficking. PMID:23248581

  9. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    Science.gov (United States)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  10. Divergent evolution of two corticotropin-releasing hormone (CRH) genes in teleost fishes.

    Science.gov (United States)

    Grone, Brian P; Maruska, Karen P

    2015-01-01

    Genome duplication, thought to have happened twice early in vertebrate evolution and a third time in teleost fishes, gives rise to gene paralogs that can evolve subfunctions or neofunctions via sequence and regulatory changes. To explore the evolution and functions of corticotropin-releasing hormone (CRH), we searched sequenced teleost genomes for CRH paralogs. Our phylogenetic and synteny analyses indicate that two CRH genes, crha and crhb, evolved via duplication of crh1 early in the teleost lineage. We examined the expression of crha and crhb in two teleost species from different orders: an African cichlid, Burton's mouthbrooder, (Astatotilapia burtoni; Order Perciformes) and zebrafish (Danio rerio; Order Cypriniformes). Furthermore, we compared expression of the teleost crha and crhb genes with the crh1 gene of an outgroup to the teleost clade: the spotted gar (Lepisosteus oculatus). In situ hybridization for crha and crhb mRNA in brains and eyes revealed distinct expression patterns for crha in different teleost species. In the cichlid, crha mRNA was found in the retina but not in the brain. In zebrafish, however, crha mRNA was not found in the retina, but was detected in the brain, restricted to the ventral hypothalamus. Spotted gar crh1 was found in the retina as well as the brain, suggesting that the ancestor of teleost fishes likely had a crh1 gene expressed in both retina and brain. Thus, genome duplication may have freed crha from constraints, allowing it to evolve distinct sequences, expression patterns, and likely unique functions in different lineages.

  11. Corticotropin-releasing hormone receptor 1 gene variants in irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Naoko Sato

    Full Text Available BACKGROUND: Corticotropin-releasing hormone (CRH acts mainly via the CRH receptor 1 (CRH-R1 and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS. Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients. METHODS: A total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402 were genotyped. Subjects' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale. RESULTS: The TT genotype of rs7209436 (P = 0.01 and rs242924 (P = 0.02 was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms and the T allele of rs7209436 (P = 0.008, T allele of rs242924 (P = 0.019, A allele of rs110402 (P = 0.047, and TAT haplocopies (P = 0.048. Negative emotion was not associated with the examined CRH-R1 SNPs. CONCLUSION: These findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted.

  12. Corticotropin-releasing hormone and the hypothalamic-pituitary-adrenal axis in psychiatric disease.

    Science.gov (United States)

    Naughton, Marie; Dinan, Timothy G; Scott, Lucinda V

    2014-01-01

    Since the 1960s, both corticotropin-releasing hormone (CRH) and the hypothalamic-pituitary-adrenal (HPA) axis have been studied in detail across a range of psychiatric illnesses, leading to important contributions to our knowledge in this area. This research arose from the conceptualization of depression, in particular, as a stress-related disorder. However, stress is now regarded as an integral component of psychiatric illnesses in general, whether as an environmental trigger or in the initial pathogenesis, and there is evidence of altered HPA axis function across a range of mental disorders. The chapter will cover the extensive literature on HPA axis abnormalities in these disorders with a particular emphasis on the CRH system as it is very evident that this 41-amino acid-containing peptide is not only a major physiologic regulator of HPA axis activity but also important in the pathogenesis of mental disorders. In particular, we discuss the abundant reports pertaining to major depressive disorder, where hyperactivity of the HPA axis, of mild to moderate severity, has been demonstrated in 30-50% of cases. Also under consideration is the less extensively studied, but equally intriguing question of HPA axis integrity in bipolar affective disorder. In addition there will be a concise summary of recent findings in schizophrenia and anxiety disorders, with an emphasis on post-traumatic stress disorder (PTSD) in the latter case. Interestingly, in diametric opposition to the theory of HPA hyperactivity in depression, PTSD has features consistent with hypofunctioning of this system. Advances in animal and human studies have made it possible to synthesize these findings, and while much still remains unknown, we are gradually building up a clearer picture of this very important axis in health, at times of stress, and in chronic enduring mental illness. © 2014 Elsevier B.V. All rights reserved.

  13. Active immunization against gonadotrophin-releasing hormone in Chinese male pigs.

    Science.gov (United States)

    Zeng, X Y; Turkstra, J A; van de Wiel, D F; Guo, D Z; Liu, X Y; Meloen, R H; Schaaper, W M; Chen, F Q; Oonk, H B; Zhang, X

    2001-04-01

    We have investigated, under the normal conditions of local Chinese pig farming, castration of young male pigs by vaccination with a newly developed vaccine against gonadotrophin releasing hormone (GnRH). Because of the very early onset of puberty, long fattening period and relatively harsh circumstances in Chinese pig production, an investigation of the endocrine response of Chinese breeds to this type of vaccination was of particular interest. Fifteen crossbred boars (Yorkshire x Yanan) from three different litters were randomly assigned to three groups of five animals each. The first group was immunized at 13 weeks of age with a GnRH tandem dimer OVA-conjugate in Specol and received a booster immunization 8 weeks later. The second group was injected with Specol alone and served as untreated controls. The remaining group was surgically castrated at the time of weaning (at 6 weeks of age). Pigs were fed ad libitum from weaning onwards. All animals were slaughtered at 31 weeks of age. Immunized boars had undetectable or low serum testosterone (0.09 +/- 0.12 ng/ml), low fat androstenone (0.05 +/- 0.01 microg/g) levels and very low testes weights (19.1 +/- 4.3 g). Intact controls had much higher serum levels of testosterone (9.76 +/- 4.81 ng/ml), fat androstenone levels (2.26 +/- 0.87 microg/g) and testes weights (114.3 +/- 29.41 g) at slaughter. Both the immunized and castrated group grew significantly faster than intact boars (p immunized, castrated and intact animals were 0.69 +/- 0.08, 0.63 +/- 0.05 and 0.42 +/- 0.07 kg (mean +/- SD), respectively. The present data demonstrate for the first time that the newly developed anti-GnRH vaccine works very well under practical Chinese pig farming conditions, and can be an attractive alternative to surgical castration.

  14. The genes associated with gonadotropin-releasing hormone-dependent precocious puberty

    Directory of Open Access Journals (Sweden)

    Jin Soon Hwang

    2012-01-01

    Full Text Available Human puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and is influenced by both environmental and genetic factors. The key genes of pubertal onset, KISS1, GPR54, GNRH1 and GNRHR, may be major causal factors underlying gonadotropin-releasing hormonedependent precocious puberty (GDPP. Two gain-of-function mutations in KISS1 and GPR54 have been identified recently as genetic causes of GDPP. GNRH1 and GNRHR are also gene candidates for GDPP; however no mutations have been identified in these genes. Presently potential genetic causes like LIN28B continues to appear; many areas of research await exploration in this context. In this review, I focus primarily on the genetic causes of GDPP.

  15. Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.

    Science.gov (United States)

    Sala, Elisa; Ferrante, Emanuele; Verrua, Elisa; Malchiodi, Elena; Mantovani, Giovanna; Filopanti, Marcello; Ferrero, Stefano; Pietrabissa, Andrea; Vanoli, Alessandro; La Rosa, Stefano; Zatelli, Maria C; Beck-Peccoz, Paolo; Verga, Uberta

    2013-07-01

    The objective of this study was to describe a multiple endocrine neoplasia type 1 (MEN1) family characterized by primary hyperparathyroidism, in association with acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion by a pancreatic neuroendocrine tumor in a young man and with a bronchial carcinoid in his mother. We investigate the clinical, radiological imaging, histopathologic findings, and therapy. An 18-year-old man successfully underwent subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic analysis showed a MEN1 gene mutation. Three years later, acromegaly because of ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH levels). A search for an ectopic tumor was unsuccessful and somatostatin analog therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal status was normalized. Afterwards, the evaluation of the patient's mother, carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm lung mass. The patient underwent subtotal pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid. In conclusion, an atypical phenotype may be recorded in MEN1 families, thus emphasizing the importance of the new imaging and surgical techniques in the diagnosis and treatment of such a rare disease.

  16. The incretin approach for diabetes treatment: modulation of islet hormone release by GLP-1 agonism

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Ørskov, Cathrine

    2004-01-01

    Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion, gene expression, and beta-cell growth. Together with the related hormone glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect, the augmentation of insulin secretion after ora...

  17. Effect of bombesin and related peptides on the release and action of intestinal hormones on pancreatic secretion.

    Science.gov (United States)

    Konturek, S J; Król, R; Tasler, J

    1976-01-01

    1. Pancreatic volume flow as well as bicarbonate and protein secretion from pancreatic fistulas have been measured in response to i.v. infusion of graded doses of bombesin and related peptides containing the COOH-terminal fragment of the bombesin molecule in conscious dogs with intact antrum and in anaesthetized animals with antrectomy, or antrectomy and enterectomy. 2. Bombesin and related peptides given to conscious dogs produced a potent and dose-dependent increase in pancreatic protein output reaching a maximum equal to that induced by the octapeptide of cholecystokinin (OP-CCK) as well as a small rise in bicarbonate output attaining a peak amounting to about 10% of that evoked by secretin. The serum gastrin level rose progressively during the infusion of bombesin to reach a peak with the highest dose of peptide. 3. Bombesin infused i.v. in anaesthetized animals with resected antrum also evoked a marked increase in pancreatic protein secretion without significant changes in the serum gastrin level. Following the removal of the antrum and small intestine, bombesin failed to show any stimulation of the pancreatic secretion or any change in the serum gastrin level. It is concluded that the strong stimulatory action of bombesin and related peptides on pancreatic secretion cannot be entirely ascribed to the release of gastrin but might be attributed at least in part to the release of intestinal hormones, particularly CCK. 4. Atropine and the growth hormone-release inhibiting hormone (GH-RIH), which were shown to inhibit the release of CCK induced by duodenal perfusion of an amino acid mixture, also caused the inhibition of pancreatic protein secretion by bombesin but failed to affect the pancreatic response to OP-CCK. The results indicate that bombesin releases, in addition to gastrin, CCK from the gut by a mechanism largely dependent upon cholingeric innervation. PMID:950608

  18. Hormonal contraception as a risk factor for obesity

    Directory of Open Access Journals (Sweden)

    Sri Sugiharti

    2005-09-01

    Full Text Available Hormonal contraception is related to change in the metabolism of some nutrients that may lead to an increase in body weight. The aims of this study is to assess the risk of obesity in hormonal contraceptive users in the District of Kulon Progo, Jogjakarta, Indonesia. A cross sectional study was used to determine the prevalence of obesity among users of contraception. A systematic cluster random sampling, using villages as clusters, was used to choose 647 users of contraception in Kulon Progo.  A hundred and two obese cases and 102 control, matched-for-age and socioeconomic status, controls were included in the case control study used to evaluate the risk of obesity among users of hormonal contraception. The prevalence of obesity among users of contraception in Kulon Progo was 15.9%. Users of hormonal contraception has a increased risk for obesity, OR: 9.4 (95% CI: 1.1 – 81.5. Users of combination pills faced the highest risk, followed by users of injected progesterone depot, while the risk in implant users was the same as that in users of non-hormonal contraception. The risk of obesity was significantly higher after 7 years of hormonal contraception use. The risk of obesity was neither related to energy intake nor expenditure. The increased risk of obesity in users of hormonal contraception was still significant after controlling for age, parity, initial weight, socioeconomic status, energy intake and expenditure, and parental obesity. We conclude that the risk of obesity is higher in users of hormonal contraception compared to the non-hormonal ones. Users of combination pills face the highest risk of obesity. (Med J Indones 2005; 14: 163-8Keywords: hormonal contraception, family planning, obesity, case control study

  19. Candidate genes associated with testicular development, sperm quality, and hormone levels of inhibin, luteinizing hormone, and insulin-like growth factor 1 in Brahman bulls.

    Science.gov (United States)

    Fortes, Marina R S; Reverter, Antonio; Hawken, Rachel J; Bolormaa, Sunduimijid; Lehnert, Sigrid A

    2012-09-01

    Bull fertility is an important target for genetic improvement, and early prediction using genetic markers is therefore a goal for livestock breeding. We performed genome-wide association studies to identify genes associated with fertility traits measured in young bulls. Data from 1118 Brahman bulls were collected for six traits: blood hormone levels of inhibin (IN) at 4 mo, luteinizing hormone (LH) following a gonadotropin-releasing hormone challenge at 4 mo, and insulin-like growth factor 1 (IGF1) at 6 mo, scrotal circumference (SC) at 12 mo, ability to produce sperm (Sperm) at 18 mo, and percentage of normal sperm (PNS) at 24 mo. All the bulls were genotyped with the BovineSNP50 chip. Sires and dams of the bull population (n = 304) were genotyped with the high-density chip (∼800 000 polymorphisms) to allow for imputation, thereby contributing detail on genome regions of interest. Polymorphism associations were discovered for all traits, except for Sperm. Chromosome 2 harbored polymorphisms associated with IN. For LH, associated polymorphisms were located in five different chromosomes. A region of chromosome 14 contained polymorphisms associated with IGF1 and SC. Regions of the X chromosome showed associations with SC and PNS. Associated polymorphisms yielded candidate genes in chromosomes 2, 14, and X. These findings will contribute to the development of genetic markers to help select cattle with improved fertility and will lead to better annotation of gene function in the context of reproductive biology.

  20. Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

    Directory of Open Access Journals (Sweden)

    Jeremy YC Teoh

    2015-06-01

    Full Text Available We investigated the cardiovascular thrombotic risk after surgical castration (SC versus gonadotropin-releasing hormone agonists (GnRHa in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years was significantly higher than the GnRHa group (71.8 ± 8.3 years (P < 0.001. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P = 0.014. Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P< 0.001, hyperlipidemia (HR 2.455, 95% CI 1.53-3.93, P< 0.001, and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031 were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

  1. Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study

    NARCIS (Netherlands)

    Braem, M.G.M.; Onland-Moret, N.C.; Brandt, P.A. van den; Goldbohm, R.A.; Peeters, P.H.M.; Kruitwagen, R.F.P.M.; Schouten, L.J.

    2010-01-01

    Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian

  2. Effect of thyrotropin releasing hormone and some of its histidine analogs on the cardiovascular system and prolactin release in the conscious rat

    OpenAIRE

    Sirén, Anna-Leena; Feuerstein, G.; Labroo, V. M.; Coleen, L. A.; Lozovsky, D.

    2012-01-01

    The cardiovascular and endocrine activity of three analogs of thyrotropin releasing hor.mone (TRH), 4-nitro-imidazole TRH (4-nitroTRH), 2-trifluoro-methyl-imidazole TRH (2-TFM-TRH) and 4-trifluoromethyl- imidazole TRH (4-TFM-TRH), was compared to TRH in conscious rats. Injection of TRH or the three analogs (1 mg/kg or 5 mg/kg) into the arterial line induced increases in mean arterial pressure, pulse pressure and heart rate and raised plasma prolactin (PRL). None of the analogs were more poten...

  3. Editorial Foreword: Comments on "Growth hormone (GH-releasing hormone and GH secretagogues in normal aging" || FREE PAPER ||

    Directory of Open Access Journals (Sweden)

    Richard F Walker

    2008-03-01

    Full Text Available Richard F WalkerInternational Society for Applied Research in Aging (SARAThis issue of Clinical Interventions in Aging contains a quite interesting and informative article about a topic that is popular and also controversial among practitioners of age-management medicine. Appropriate to that controversy, Drs Hersch and Merriam (2008 have asked the question in the title of their paper, does the use of growth hormone secretagogues in age management medicine hold the promise of a fountain of youth, or that of a pool of Tantalus? While there is universal understanding of the fountain imagery, the meaning of the pool is perhaps less obvious. It derives, of course, from the Greek myth of Tantalus, who had both a hidden, divine sire and a mortal one. As the son of Zeus, he was uniquely favored among mortals and was invited to share the food of the gods. However, driven by pride, he shared the divine ambrosia with other mortals, and thus aroused the ire of the gods. As punishment, he was made to stand chin-deep in water with a variety of sweet-smelling and delicious fruit dangling just over his head. However, whenever he tried to drink or eat, the water would magically recede or the fruit would miraculously be lifted just out of his reach. Thus, it is that torment, through which something seems to be offered only to be withdrawn again, that has been called “tantalizing” in memory of its best known victim.

  4. Regulation of corticotropin releasing hormone receptor type 1 messenger RNA level in Y-79 retinoblastoma cells: potential implications for human stress response and immune/inflammatory reaction

    Directory of Open Access Journals (Sweden)

    N. C. Vamvakopoulos

    1996-01-01

    Full Text Available We report the regulation of type 1 receptor mRNA in Y-79 human retinoblastoma cells, grown in the absence or presence of pharmacological levels of phorbol esters, forskolin, glucocorticoids and their combinations. To control for inducibility and for assessing the sensitivity of the Y-79 system to glucocorticoids, corticotropin releasing hormone mRNA levels were measured in parallel. All treatments stimulated corticotropin releasing hormone receptor type 1 gene expression relative to baseline. A weak suppression of corticotropin releasing hormone mRNA level was observed during dexamethasone treatment. The cell line expressed ten-fold excess of receptor to ligand mRNA under basal conditions. The findings predict the presence of functional phorbol ester, cyclic AMP and glucocorticoid response elements in the promoter region of corticotropin releasing hormone receptor type 1 gene and support a potential role for its product during chronic stress and immune/inflammatory reaction.

  5. Ocular findings in adult subjects with an inactivating mutation in GH releasing hormone receptor gene.

    Science.gov (United States)

    Faro, Augusto C N; Pereira-Gurgel, Virginia M; Salvatori, Roberto; Campos, Viviane C; Melo, Gustavo B; Oliveira, Francielle T; Oliveira-Santos, Alecia A; Oliveira, Carla R P; Pereira, Francisco A; Hellström, Ann; Oliveira-Neto, Luís A; Valença, Eugenia H O; Aguiar-Oliveira, Manuel H

    2017-06-01

    Ocular function is fundamental for environmental adaptation and survival capacity. Growth factors are necessary for a mature eyeball, needed for adequate vision. However, the consequences of the deficiency of circulating growth hormone (GH) and its effector insulin-like growth factor I (IGF-I) on the physical aspects of the human eye are still debated. A model of untreated isolated GH deficiency (IGHD), with low but measurable serum GH, may clarify this issue. The aim of this study was to assess the ocular aspects of adult IGHD individuals who have never received GH therapy. Cross sectional study. Setting: University Hospital, Federal University of Sergipe, Brazil. Twenty-five adult (13 males, mean age 50.1years, range 26 to 70years old) IGHD subjects homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene, and 28 (15 males, mean age 51.1years, range 26 to 67years old) controls were submitted to an endocrine and ophthalmological assessment. Forty-six IGHD and 50 control eyes were studied. Visual acuity, intraocular pressure, refraction (spherical equivalent), ocular axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous depth (VD), mean corneal curvature (CC) and central corneal thickness (CCT). IGHD subjects exhibited unmeasurable serum IGF-I levels, similar visual acuity, intraocular pressure and LT, higher values of spherical equivalent and CC, and lower measures of AL, ACD, VD and CCT in comparison to controls, but within their respective normal ranges. While mean stature in IGHD group was 78% of the control group, mean head circumference was 92% and axial AL was 96%. These observations suggest mild ocular effects in adult subjects with severe IGF-I deficiency due to non-treated IGHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Gonadotropin-Releasing Hormone (GnRH) Receptor Structure and GnRH Binding.

    Science.gov (United States)

    Flanagan, Colleen A; Manilall, Ashmeetha

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) regulates reproduction. The human GnRH receptor lacks a cytoplasmic carboxy-terminal tail but has amino acid sequence motifs characteristic of rhodopsin-like, class A, G protein-coupled receptors (GPCRs). This review will consider how recent descriptions of X-ray crystallographic structures of GPCRs in inactive and active conformations may contribute to understanding GnRH receptor structure, mechanism of activation and ligand binding. The structures confirmed that ligands bind to variable extracellular surfaces, whereas the seven membrane-spanning α-helices convey the activation signal to the cytoplasmic receptor surface, which binds and activates heterotrimeric G proteins. Forty non-covalent interactions that bridge topologically equivalent residues in different transmembrane (TM) helices are conserved in class A GPCR structures, regardless of activation state. Conformation-independent interhelical contacts account for a conserved receptor protein structure and their importance in the GnRH receptor structure is supported by decreased expression of receptors with mutations of residues in the network. Many of the GnRH receptor mutations associated with congenital hypogonadotropic hypogonadism, including the Glu2.53(90) Lys mutation, involve amino acids that constitute the conserved network. Half of the ~250 intramolecular interactions in GPCRs differ between inactive and active structures. Conformation-specific interhelical contacts depend on amino acids changing partners during activation. Conserved inactive conformation-specific contacts prevent receptor activation by stabilizing proximity of TM helices 3 and 6 and a closed G protein-binding site. Mutations of GnRH receptor residues involved in these interactions, such as Arg3.50(139) of the DRY/S motif or Tyr7.53(323) of the N/DPxxY motif, increase or decrease receptor expression and efficiency of receptor coupling to G protein signaling, consistent with the native residues

  7. Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals

    Directory of Open Access Journals (Sweden)

    Amy T. Desaulniers

    2017-12-01

    Full Text Available Gonadotropin-releasing hormone 1 (GnRH1 and its receptor (GnRHR1 drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2 and its receptor (GnRHR2 also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat or inactivated (e.g., cow and sheep in some species but retained in others (e.g., human, horse, and pig. Likewise, many species (e.g., human, chimpanzee, cow, and sheep retain the GnRHR2 gene but lack the appropriate coding sequence to produce a full-length protein due to gene coding errors; although production of GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene (e.g., mouse or most exons entirely (e.g., rat. In contrast, old world monkeys, musk shrews, and pigs maintain the coding sequence required to produce a functional GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor that interacts with Gαq/11 to mediate cell signaling. However, GnRHR2 retains a cytoplasmic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor in mammals has been elusive, likely because common laboratory models lack both the ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the interaction between nutritional status and sexual behavior in the female brain. Within peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. In the female, GnRH2 and

  8. Synthesis, receptor binding, and CNS pharmacological studies of new thyrotropin-releasing hormone (TRH) analogues.

    Science.gov (United States)

    Monga, Vikramdeep; Meena, Chhuttan L; Rajput, Satyendra; Pawar, Chandrashekhar; Sharma, Shyam S; Lu, Xinping; Gershengorn, Marvin C; Jain, Rahul

    2011-03-07

    As part of our search for selective and CNS-active thyrotropin-releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH-R1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH-R1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 a (R=CH3) exhibited binding affinities (Ki values) of 0.17 μM for TRH-R1 and 0.016 μM for TRH-R2; it is 10-fold less potent than TRH in binding to TRH-R1 and equipotent with TRH in binding to TRH-R2. Compound 21 a, the most selective agonist, activated TRH-R2 with a potency (EC50 value) of 0.0021 μM, but activated TRH-R1 at EC50=0.05 μM, and exhibited 24-fold selectivity for TRH-R2 over TRH-R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate-induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21 a,b and 22 a,b decreased sleeping time by nearly 50% more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ-induced seizures, but failed to provide any protection in MES-induced seizures at 10 μmol kg(-1). The results of this study provide evidence that TRH analogues that show selectivity for TRH-R2 over TRH-R1 possess potent CNS activity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome.

    Directory of Open Access Journals (Sweden)

    Hazuki Komuro

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in the pathophysiology of irritable bowel syndrome (IBS and regulates the stress response through two CRH receptors (R1 and R2. Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436 and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220 were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017 and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS, and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710 and two SNPs (rs2284217 and rs2284220 in strong linkage disequilibrium (D' > 0.90. We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH

  10. A possible role of SchistoFLRFamide in inhibition of adipokinetic hormone release from locust corpora cardiaca.

    Science.gov (United States)

    Vullings, H G; Ten Voorde, S E; Passier, P C; Diederen, J H; Van Der Horst, D J; Nässel, D R

    1998-12-01

    The distribution and actions of FMRFamide-related peptides (FaRPs) in the corpora cardiaca of the locust Locusta migratoria were studied. Antisera to FMRFamide and SchistoFLRFamide (PDVDHVFLRFamide) label neuronal processes that impinge on glandular cells in the glandular lobe of the corpora cardiaca known to produce adipokinetic hormones. Electron microscopic immunocytochemistry revealed that these FaRP-containing processes form synaptoid contacts with the glandular cells. Approximately 12% of the axon profiles present in the glandular part of the corpus cardiacum contained SchistoFLRFamide-immunoreactive material. Retrograde tracing of the axons in the nervus corporis cardiaci II with Lucifer yellow revealed 25-30 labelled neuronal cell bodies in each lateral part of the protocerebrum. About five of these in each hemisphere reacted with the SchistoFLRFamide-antiserum. Double-labelling immunocytochemistry showed that the FaRP-containing processes in the glandular lobe of the corpora cardiaca are distinct from neuronal processes, reacting with an antiserum to the neuropeptide locustatachykinin. The effect of the decapeptide SchistoFLRFamide and the tetrapeptide FMRFamide on the release of adipokinetic hormone I (AKH I) from the cells in the glandular part of the corpus cardiacum was studied in vitro. Neither the deca- nor the tetrapeptide had any effect on the spontaneous release of AKH I. Release of AKH I induced by the phosphodiesterase inhibitor IBMX, however, was reduced significantly by both peptides. These results point to an involvement of FaRPs as inhibitory modulators in the regulation of the release of adipokinetic hormone from the glandular cells.

  11. Hormonal and Growth Factor Responses to Heavy Resistance Exercise Protocols

    Science.gov (United States)

    1990-01-01

    calculated as weight periods. The load control workout for series I used a 10- times the vertical distance moved per repetition times RM load and was... time of day to reduce the effects of any diurnal variations on the RESULTS hormonal concentrations. Before a resting blood sample was obtained, a 20...sustained elevations over time . In contrast, creases in hormonal responses previously thought to alterations in serum testosterone and somatomedin-C

  12. Treatment of Paraphilic Disorders in Sexual Offenders or Men With a Risk of Sexual Offending With Luteinizing Hormone-Releasing Hormone Agonists: An Updated Systematic Review.

    Science.gov (United States)

    Turner, Daniel; Briken, Peer

    2018-01-01

    Different pharmacologic agents are used in the treatment of paraphilic disorders in sexual offenders or men with a risk of sexual offending, with luteinizing hormone-releasing hormone (LHRH) agonists being the agents introduced more recently to treatment regimens. To summarize the relevant literature concerning LHRH agonist treatment of paraphilic disorders in sexual offenders and update the previously published systematic review by Briken et al (J Clin Psychiatry 2003;64:890-897). The PubMed and Google Scholar databases were searched for literature published from January 2003 through October 2017 using the following key words: LHRH agonists, GnRH agonists, antiandrogens AND paraphilia, pedophilia, sex offenders. Evaluation of the effectiveness and side effects of LHRH agonist treatment of paraphilic disorders in sexual offenders. After screening for duplicates and applying specific selection criteria, the search yielded 24 eligible studies reporting on a sample of 256 patients. There is increasing evidence that LHRH agonists are more effective than steroidal antiandrogens in lowering paraphilic sexual thoughts and behaviors. Current research also is based on methods that might be less susceptible to faking (eg, eye-tracking, brain imaging, and viewing-time measures). Side effects occurring most frequently are fatigue, hot flashes, depressive mood, weight gain, high blood pressure, diabetes, gynecomastia, loss of erectile function, and loss of bone mineral density. Although LHRH agonists seem to be the most effective drugs in the treatment of paraphilic fantasies and behaviors, they should be reserved for patients with a paraphilic disorder and the highest risk of sexual offending because of their extensive side effects. This systematic review considers all types of research on LHRH agonist treatment in patients with paraphilic disorders, thereby providing a complete overview of the current state of research. However, most studies are case reports or observational

  13. 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

  14. Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation.

    Science.gov (United States)

    Luo, LuGuang; Luo, John Z Q; Jackson, Ivor

    2013-02-01

    A very small tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropin-Releasing Hormone, TRH), was first identified in the brain hypothalamus area. Further studies found that L-PHP was expressed in pancreas. The biological role of pancreatic L-PHP is still not clear. Growing evidence indicates that L-PHP expression in the pancreas may play a pivotal role for pancreatic development in the early prenatal period. However, the role of L-PHP in adult pancreas still needs to be explored. L-PHP activation of pancreatic β cell Ca2+ flow and stimulation of β-cell insulin synthesis and release suggest that L-PHP involved in glucose metabolism may directly act on the β cell separate from any effects via the central nervous system (CNS). Knockout L-PHP animal models have shown that loss of L-PHP expression causes hyperglycemia, which cannot be reversed by administration of thyroid hormone, suggesting that the absence of L-PHP itself is the cause. L-PHP receptor type-1 has been identified in pancreas which provides a possibility for L-PHP autocrine and paracrine regulation in pancreatic function. During pancreatic damage in adult pancreas, L-PHP may protect beta cell from apoptosis and initiate its regeneration through signal pathways of growth hormone in β cells. L-PHP has recently been discovered to affect a broad array of gene expression in the pancreas including growth factor genes. Signal pathways linked between L-PHP and EGF receptor phosphorylation suggest that L-PHP may be an important factor for adult β-cell regeneration, which could involve adult stem cell differentiation. These effects suggest that L-PHP may benefit pancreatic β cells and diabetic therapy in clinic.

  15. 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

  16. 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

  17. Modeling and high-throughput experimental data uncover the mechanisms underlying Fshb gene sensitivity to gonadotropin-releasing hormone pulse frequency.

    Science.gov (United States)

    Stern, Estee; Ruf-Zamojski, Frederique; Zalepa-King, Lisa; Pincas, Hanna; Choi, Soon Gang; Peskin, Charles S; Hayot, Fernand; Turgeon, Judith L; Sealfon, Stuart C

    2017-06-09

    Neuroendocrine control of reproduction by brain-secreted pulses of gonadotropin-releasing hormone (GnRH) represents a longstanding puzzle about extracellular signal decoding mechanisms. GnRH regulates the pituitary gonadotropin's follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of which are heterodimers specified by unique β subunits (FSHβ/LHβ). Contrary to Lhb, Fshb gene induction has a preference for low-frequency GnRH pulses. To clarify the underlying regulatory mechanisms, we developed three biologically anchored mathematical models: 1) parallel activation of Fshb inhibitory factors (e.g. inhibin α and VGF nerve growth factor-inducible), 2) activation of a signaling component with a refractory period (e.g. G protein), and 3) inactivation of a factor needed for Fshb induction (e.g. growth differentiation factor 9). Simulations with all three models recapitulated the Fshb expression levels obtained in pituitary gonadotrope cells perifused with varying GnRH pulse frequencies. Notably, simulations altering average concentration, pulse duration, and pulse frequency revealed that the apparent frequency-dependent pattern of Fshb expression in model 1 actually resulted from variations in average GnRH concentration. In contrast, models 2 and 3 showed "true" pulse frequency sensing. To resolve which components of this GnRH signal induce Fshb, we developed a high-throughput parallel experimental system. We analyzed over 4,000 samples in experiments with varying near-physiological GnRH concentrations and pulse patterns. Whereas Egr1 and Fos genes responded only to variations in average GnRH concentration, Fshb levels were sensitive to both average concentration and true pulse frequency. These results provide a foundation for understanding the role of multiple regulatory factors in modulating Fshb gene activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning.

    Science.gov (United States)

    Bogdan, Ryan; Santesso, Diane L; Fagerness, Jesen; Perlis, Roy H; Pizzagalli, Diego A

    2011-09-14

    Stress is a general risk factor for psychopathology, but the mechanisms underlying this relationship remain largely unknown. Animal studies and limited human research suggest that stress can induce anhedonic behavior. Moreover, emerging data indicate that genetic variation within the corticotropin-releasing hormone type 1 receptor gene (CRHR1) at rs12938031 may promote psychopathology, particularly in the context of stress. Using an intermediate phenotypic neurogenetics approach, we assessed how stress and CRHR1 genetic variation (rs12938031) influence reward learning, an important component of anhedonia. Psychiatrically healthy female participants (n = 75) completed a probabilistic reward learning task during stress and no-stress conditions while 128-channel event-related potentials were recorded. Fifty-six participants were also genotyped across CRHR1. Response bias, an individual's ability to modulate behavior as a function of reward, was the primary behavioral variable of interest. The feedback-related positivity (FRP) in response to reward feedback was used as a neural index of reward learning. Relative to the no-stress condition, acute stress was associated with blunted response bias as well as a smaller and delayed FRP (indicative of disrupted reward learning) and reduced anterior cingulate and orbitofrontal cortex activation to reward. Critically, rs12938031 interacted with stress to influence reward learning: both behaviorally and neurally, A homozygotes showed stress-induced reward learning abnormalities. These findings indicate that acute, uncontrollable stressors reduce participants' ability to modulate behavior as a function of reward, and that such effects are modulated by CRHR1 genotype. Homozygosity for the A allele at rs12938031 may increase risk for psychopathology via stress-induced reward learning deficits.

  19. Lack of pulse and surge modes and glutamatergic stimulation of luteinising hormone release in Kiss1 knockout rats.

    Science.gov (United States)

    Uenoyama, Y; Nakamura, S; Hayakawa, Y; Ikegami, K; Watanabe, Y; Deura, C; Minabe, S; Tomikawa, J; Goto, T; Ieda, N; Inoue, N; Sanbo, M; Tamura, C; Hirabayashi, M; Maeda, K-I; Tsukamura, H

    2015-03-01

    Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate neuropeptide in controlling puberty and reproduction via regulation of gonadotrophin-releasing hormone (GnRH) secretion in mammals. Pioneer studies with Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable role of kisspeptin-GPR54 signalling in the control of animal reproduction, although detailed analyses of gonadotrophin secretion, especially pulsatile and surge-mode of luteinising hormone (LH) secretion, were limited. Thus, in the present study, we have generated Kiss1 KO rats aiming to evaluate a key role of kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH secretion. Kiss1 KO male and female rats showed a complete suppression of pulsatile LH secretion, which is responsible for folliculogenesis and spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female rats showed no spontaneous LH/follicle-stimulating hormone surge and an oestrogen-induced LH surge, suggesting that the GnRH surge generation system, which is responsible for ovulation, does not function without kisspeptin. Furthermore, challenge of major stimulatory neurotransmitters, such as monosodium glutamate, NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats, albeit they stimulated LH release in wild-type controls. Taken together, the results of the present study confirm that kisspeptin plays an indispensable role in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to regulate puberty onset and normal reproductive performance. In addition, the present study suggests that kisspeptin neurones play a critical role as a hub integrating major stimulatory neural inputs to GnRH neurones, using newly established Kiss1 KO rats, which serve as a useful model for detailed analysis of hormonal profiles. © 2015 British Society for Neuroendocrinology.

  20. 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.

  1. The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

    Science.gov (United States)

    Rosario, Derek J; Davey, Patrick; Green, James; Greene, Damien; Turner, Bruce; Payne, Heather; Kirby, Mike

    2016-12-01

    Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease.

  2. Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist

    Directory of Open Access Journals (Sweden)

    Wignall Jacqui

    2010-04-01

    Full Text Available Abstract Background It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs. There is a need for simple, cost-effective alternative techniques to induce spawning. Methods Our new method is based on the injection of a combination of a gonadotropin-releasing hormone (GnRH agonist and a dopamine antagonist. We have named this formulation AMPHIPLEX, which is derived from the combination of the words amphibian and amplexus. This name refers to the specific reproductive behavior of frogs when the male mounts and clasps the female to induce ovulation and to fertilize the eggs as they are laid. Results We describe the use of the method and demonstrate its applicability for captive breeding in 3 different anuran families. We tested several combinations of GnRH agonists with dopamine antagonists using Lithobates pipiens. The combination of des-Gly10, D-Ala6, Pro-LHRH (0.4 microrams/g body weight and metoclopramide (10 micrograms/g BWt. MET was most effective. It was used in-season, after short-term captivity and in frogs artificially hibernated under laboratory conditions. The AMPHIPLEX method was also effective in 3 Argentinian frogs, Ceratophrys ornata, Ceratophrys cranwelli and Odontophrynus americanus. Conclusion Our approach offers some advantages over other hormonally-based techniques. Both sexes are injected only once and at the same time, reducing handling stress. AMPHIPLEX is a new reproductive management tool for captive breeding in Anura.

  3. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Directory of Open Access Journals (Sweden)

    Nikolaos Kyriakakis

    2017-01-01

    Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.

  4. Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression.

    Science.gov (United States)

    Wu, Hsien-Ming; Huang, Hong-Yuan; Schally, Andrew V; Chao, Angel; Chou, Hung-Hsueh; Leung, Peter C K; Wang, Hsin-Shih

    2017-01-17

    More than 25% of patients diagnosed with endometrial carcinoma have invasive primary cancer accompanied by metastases. Growth hormone-releasing hormone (GHRH) plays an important role in reproduction. Here, we examined the effect of a GHRH antagonist on the motility of endometrial cancer cells and the mechanisms of action of the antagonist in endometrial cancer. Western blotting and immunohistochemistry (IHC) were used to determine the expression of the GHRH receptor protein. The activity of Twist and N-cadherin was determined by Western blotting. Cell motility was assessed by an invasion and migration assay. GHRH receptor siRNA was applied to knockdown the GHRH receptor in endometrial cancer cells. The GHRH antagonist inhibited cell motility in a dose-dependent manner. The GHRH antagonist inhibited cell motility and suppressed the expression of Twist and N-cadherin, and the suppression was abolished by GHRH receptor siRNA pretreatment. Moreover, the inhibition of Twist and N-cadherin with Twist siRNA and N-cadherin siRNA, respectively, suppressed cell motility. Our study indicates that the GHRH antagonist inhibited the cell motility of endometrial cancer cells through the GHRH receptor via the suppression of Twist and N-cadherin. Our findings represent a new concept in the mechanism of GHRH antagonist-suppressed cell motility in endometrial cancer cells and suggest the possibility of exploring GHRH antagonists as potential therapeutics for the treatment of human endometrial cancer.

  5. Risk factors for complications of open trigger finger release.

    Science.gov (United States)

    Everding, Nathan G; Bishop, Gavin B; Belyea, Christopher M; Soong, Maximillian C

    2015-06-01

    Open trigger finger release is generally considered a simple low-risk procedure. Reported complication rates vary widely from 1 to 43 %, mostly based on small studies. Our goal was to determine the incidence of complications in a large consecutive series, while also identifying potential risk factors. All open trigger finger releases performed from 2006 to 2009 by four fellowship-trained hand surgeons at a single institution were retrospectively reviewed. There were 795 digits released in 543 patients. Complications were defined as signs or symptoms requiring further treatment and/or considered unresolved by 1 month postoperatively. Complications requiring operative intervention were regarded as major. Multivariable analysis was performed to determine possible risk factors for complications. There were 95 documented complications among 795 digits (12 %). The most common complications involved persistent pain, stiffness, or swelling, persistent or recurrent triggering, or superficial infection. Most were treated nonoperatively with observation, therapy, steroid injection, or oral antibiotics. There were 19 reoperations (2.4 %), mostly including revision release, tenosynovectomy, and irrigation and debridement. Male gender, sedation, and general anesthesia were independently associated with complications, while age, diabetes, hypothyroidism, recent injection, and concurrent procedures were not associated. Open trigger finger release is generally a low-risk procedure, although there is potential for complications, some requiring reoperation. Male gender, sedation, and general anesthesia may be associated with greater risk. Surgeons should be careful to thoroughly discuss the risk of both major and minor complications when counseling patients.

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

    Directory of Open Access Journals (Sweden)

    L.O. Naumova

    2014-09-01

    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.

  7. Galactopoiesis/Effects of hormones and growth factors

    Science.gov (United States)

    The term galactopoiesis was originally coined to describe the enhancement of an established lactation. In this sense, only exogenous somatotropin and thyroid hormones are clearly demonstrated galactopoietic agents in dairy animals. However, in a more inclusive sense, galactopoiesis has been used t...

  8. Reproductive and hormonal risk factors of breast cancer: a historical perspective

    National Research Council Canada - National Science Library

    Horn J; Vatten LJ

    2017-01-01

    ...: The complexity of breast cancer etiology has puzzled scientists for more than 300 years. In this brief review, we emphasize the importance of reproductive and hormonal factors in relation to the risk of breast cancer...

  9. Uniformity of Peptide Release Is Maintained by Methylation of Release Factors

    Directory of Open Access Journals (Sweden)

    William E. Pierson

    2016-09-01

    Full Text Available Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs, which share a conserved glycine-glycine-glutamine (GGQ motif. The glutamine residue is methylated in vivo, but a mechanistic understanding of its contribution to hydrolysis is lacking. Here, we show that the modification, apart from increasing the overall rate of termination on all dipeptides, substantially increases the rate of peptide release on a subset of amino acids. In the presence of unmethylated RFs, we measure rates of hydrolysis that are exceptionally slow on proline and glycine residues and approximately two orders of magnitude faster in the presence of the methylated factors. Structures of 70S ribosomes bound to methylated RF1 and RF2 reveal that the glutamine side-chain methylation packs against 23S rRNA nucleotide 2451, stabilizing the GGQ motif and placing the side-chain amide of the glutamine toward tRNA. These data provide a framework for understanding how release factor modifications impact termination.

  10. Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane

    Science.gov (United States)

    Kim, Eung-Sam; Jang, Do Soo; Yang, Seung Yun; Lee, Mi Nam; Jin, Kyeong Sik; Cha, Hyung Jin; Kim, Jin Kon; Sung, Young Chul; Choi, Kwan Yong

    2013-05-01

    Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and

  11. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD......-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin....... This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...

  12. Controlled ovarian stimulation using a long gonadotropin-releasing hormone antagonist protocol: a proof of concept and feasibility study.

    Science.gov (United States)

    Weissman, Ariel; Ravhon, Amir; Steinfeld, Zohar; Nahum, Hana; Golan, Abraham; Levran, David

    2013-01-01

    To evaluate the feasibility of a long protocol of controlled ovarian stimulation prior to in vitro fertilization (IVF) and embryo transfer with a gonadotropin-releasing hormone (GnRH) antagonist used for pituitary and ovarian suppression. Thirty patients undergoing IVF/intracytoplasmic sperm injection were randomized into two groups. The control group (n = 16) received a standard flexible GnRH antagonist protocol. Ovarian stimulation consisted of 225 IU/day of recombinant follicle-stimulating hormone for 5 days, followed by 225 IU/day of human menopausal gonadotropin until human chorionic gonadotropin (hCG) administration. The study group (n = 14) received 0.25 mg of GnRH antagonist daily for 7 days, thereafter, upon confirmation of pituitary and ovarian suppression, ovarian stimulation was commenced with the same protocol as used in the control group. Hormone and follicle dynamics, as well as laboratory characteristics and cycle outcome, were compared for both groups. Both groups were comparable in baseline characteristics. Pituitary and ovarian suppression were effectively achieved in 12/14 patients in the study group. The duration of ovarian stimulation and gonadotropin consumption were similar in both groups, as was also the number and size of follicles on hCG day. The results of our study confirm the feasibility of a long GnRH antagonist protocol. This regimen could become another option to optimize GnRH antagonist protocols, and should thus be further explored. © 2013 S. Karger AG, Basel.

  13. [Hormonal contraception as a risk factor for developing cervical cancer: biological, epidemiological and immunological evidence].

    Science.gov (United States)

    Castro Romero, Julieta Ivone; Hernández Girón, Carlos; Madrid Marina, Vicente

    2011-09-01

    Cervical cancer has been extensively studied, as well as the various risk factors for that cancer. One such factor is the prolonged use of hormonal contraceptives. To report the biological, immunological and epidemiological findings arising from the use of oral contraceptives and their relation to cervical cancer. Retrospective study based on information published in national and international literature. Controversy persists between the epidemiological data and experimental biological association between hormonal contraceptives and cancer induced by HPV. It is important to consider the biological findings because in Mexico the use of hormonal contraceptives is very broad and the number of cases of cervical cancer and only extensive epidemiological studies will clarify this controversy.

  14. Evaluating the Genetic, Hormonal, and Exogenous Factors Affecting Somatic Copy Number Variation in Breast Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0579 TITLE: Evaluating the Genetic , Hormonal, and Exogenous Factors Affecting Somatic Copy Number Variation in...Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluating the Genetic , Hormonal, and Exogenous Factors Affecting Somatic Copy...progress in subaim 1a, substantially improving the design of our proposed transgenic animal , the “deletion reporter mouse”, and are finalizing cloning

  15. Effects of Growth Hormone–Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults

    Science.gov (United States)

    Baker, Laura D.; Barsness, Suzanne M.; Borson, Soo; Merriam, George R.; Friedman, Seth D.; Craft, Suzanne; Vitiello, Michael V.

    2013-01-01

    Background Growth hormone–releasing hormone (GHRH), growth hormone, and insulinlike growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI). Objective To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI. Design Randomized, double-blind, placebo-controlled trial. Setting Clinical Research Center, University of Washington School of Medicine in Seattle. Participants A total of 152 adults (66 with MCI) ranging in age from 55 to 87 years (mean age, 68 years); 137 adults (76 healthy participants and 61 participants with MCI) successfully completed the study. Intervention Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analog of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline, at weeks 10 and 20 of treatment, and after a 10-week washout (week 30), blood samples were collected, and parallel versions of a cognitive battery were administered. Before and after the 20-week intervention, participants completed an oral glucose tolerance test and a dual-energy x-ray absorptiometry scan to measure body composition. Main Outcome Measures Primary cognitive outcomes were analyzed using analysis of variance and included 3 composites reflecting executive function, verbal memory, and visual memory. Executive function was assessed with Stroop Color-Word Interference, Task Switching, the Self-Ordered Pointing Test, and Word Fluency, verbal memory was assessed with Story Recall and the Hopkins Verbal Learning Test, and visual memory was assessed with the Visual-Spatial Learning Test and Delayed Match

  16. 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...

  17. Evidence for a function of calcium influx in the stimulation of hormone release fron the parathyroid gland in the goat.

    Science.gov (United States)

    Hove, K; Sand, O

    1981-09-01

    The acute effects of various drugs on the release of parathyroid hormone (PTH) in goats were studied by local infusions in vivo. Infusions of Ca2+ or Sr2+ reduced the PTH secretion rate, whereas hypocalcemia induced by EDTA increased the PTH release. Blockers of voltage sensitive Ca2+ channels (verapamil, D-600 and nifedipine) lowered the PTH secretion rate, while infusion of 4-aminopyridine, which is a blocker of voltage sensitive K+ channels, increased the PTH release. These effects were not due to altered beta-adrenergic tonus, since the effects persisted when the drugs were administered during continuous infusion of the beta-blocker propranolol. We suggest that the parathyroid cells possess voltage sensitive K+ and Ca2+ channels, and that exocytosis of stored PTH depends on the influx of extracellular Ca2+ as in other secretory cells. In order to explain the inverse relationship between the plasma Ca2+ level and the PTH release, we postulate a suppressive effect of the plasma Ca2+ on the membrane permeability to Ca2+ in parathyroid cells.

  18. Fetal Exposure to Placental Corticotropin-Releasing Hormone is Associated with Child Self-Reported Internalizing Symptoms

    Science.gov (United States)

    Howland, Mariann A.; Sandman, Curt A.; Glynn, Laura M.; Crippen, Cheryl; Davis, Elysia Poggi

    2016-01-01

    Objective Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5. Method Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks’ gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview. Results Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self-reported internalizing symptoms. Conclusions Findings suggest that elevated exposures to the feto-placental stress signal pCRH exert programming effects on the developing fetal central nervous system, with lasting consequences for child mental health. PMID:26855003

  19. Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms.

    Science.gov (United States)

    Howland, Mariann A; Sandman, Curt A; Glynn, Laura M; Crippen, Cheryl; Davis, Elysia Poggi

    2016-05-01

    Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5. Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks' gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview. Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self-reported internalizing symptoms. Findings suggest that elevated exposures to the feto-placental stress signal pCRH exert programming effects on the developing fetal central nervous system, with lasting consequences for child mental health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve in rats receiving cyclophosphamide treatment

    Directory of Open Access Journals (Sweden)

    Gui T

    2015-03-01

    Full Text Available Ting Gui,1,* Guangwen Yuan,2,* Keng Shen,1 Dongyan Cao,1 Jiaxin Yang,1 Ming Wu,1 Jinghe Lang11Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 2Department of Gynecologic Oncology, Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of China*These authors contributed equally to this workObjective: The aim of the study reported here was to investigate the protective effect of gonadotropin-releasing hormone analog (GnRHa against cyclophosphamide (CTX-induced gonadotoxicity.Methods: Eighty Fischer 344 rats were divided randomly into four groups (20 per group. One group received normal saline, one GnRHa, one CTX, and one GnRHa+CTX. Several parameters were used to observe the ovarian reserve, including ovary weight, follicle number and diameter, concentrations of estradiol (E2 and follicle-stimulating hormone (FSH, and expressions of sex hormone receptors.Results: When treatment was finished, the number of small follicles in the GnRHa+CTX group was significantly higher than in the CTX-alone group. Thirty days after treatment, the ovary weight, percentage of small follicles, mean follicular diameter, and serum concentrations of E2 and FSH in the GnRHa+CTX group all recovered, approaching normal levels. Sex hormone receptors did not show significant differences between the four groups.Conclusion: Combination treatment with GnRHa could prevent CTX-induced damage to ovarian reserve.Keywords: gonadotoxicity, ovarian reserve, GnRHa, CTX, premature ovarian failure

  1. Neuronal-glial plasticity in gonadotropin-releasing hormone release in adult female rats: role of the polysialylated form of the neural cell adhesion molecule.

    Science.gov (United States)

    Parkash, Jyoti; Kaur, Gurcharan

    2005-08-01

    The gonadotropin-releasing hormone (GnRH) neurosecretory system undergoes marked structural and functional changes during the ovarian cycle. The aim of this study was to examine the neuroanatomical relationship between GnRH neurons and a polysialylated form of neural cell adhesion molecule (PSA-NCAM), a known marker of neuronal plasticity. Using immunohistofluorescent dual labeling, we determined that axon terminals of GnRH in the median arcuate nucleus (ME-ARC) region of the hypothalamus in the proestrous phase of the estrous cycle were intimately associated with PSA-NCAM. To further examine whether PSA-NCAM expression associated with GnRH neuron terminals varies in conjugation with cyclic changes in ovarian steroid hormone levels, we examined GnRH and PSA-NCAM dual expression in ovariectomized (OVX) and estrogen-progesterone-primed OVX (EBP-OVX) rats. The expression of PSA-NCAM immunoreactivity associated with the GnRH neurons in the proestrous phase and EBP-OVX rats was significantly higher than during the diestrous phase and in OVX rats where GnRH secretion declines. We further examined whether the structural changes in GnRH axon terminals in the ME-ARC region are also associated with glial plasticity. By extension and retraction of the glial processes, the GnRH neuron terminals in the ME-ARC region could undergo dynamic plastic changes that control GnRH release during the proestrous phase. PSA-NCAM expression was also seen on glial cells in the ME-ARC region. The close association between PSA-NCAM on GnRH and glial cells in the ME-ARC region of the hypothalamus in the rat showed dynamic structural changes in GnRH neuron terminals during the estrous cycle. These observations suggested that PSA-NCAM may act as a molecular substrate to promote neuroplastic changes in the GnRH neurosecretory system.

  2. Growth hormone and prolactin responses to corticotrophin-releasing-hormone in patients with Cushing's disease: a paracrine action of the adenomatous corticotrophic cells?

    Science.gov (United States)

    Loli, P; Boccardi, E; Branca, V; Bramerio, M; Barberis, M; Losa, M; Terreni, M T; Lodrini, S; Pollo, B; Vignati, F

    1998-10-01

    In patients with Cushing's disease multihormonal responses to ovine corticotrophin releasing hormone (oCRH) have been detected in blood from inferior petrosal sinuses. This finding has been explained by co-secretion of other hormones, in addition to ACTH, by the pituitary adenoma itself or by paracrine effects exerted by the adenoma on normal periadenomatous pituitary cells. To assess these hypotheses we compared the presence of a CRH induced GH and/or PRL response during inferior petrosal sinus sampling to the immunohistochemical detection of PRL and GH in adenomatous tissue removed from patients with Cushing's disease. Twenty-two patients with Cushing's disease and two patients with ectopic ACTH syndrome due to a bronchial carcinoid were studied; each patient had undergone preoperative inferior petrosal sinus sampling for diagnostic purposes with determination of GH and PRL in addition to ACTH, before and after administration of oCRH. Immunohistochemical studies for ACTH, GH and PRL detection were carried out on adenomatous tissue removed at surgery in the patients with pituitary dependent Cushing's disease and on the carcinoid tumours from the two patients with ectopic ACTH syndrome. All pituitary adenomas immunostained for ACTH, and four adenomas immunostained for GH or PRL in addition to ACTH. A PRL increase in the inferior petrosal sinus after oCRH administration was found in 11 of 22 patients, but none of their tumours immunostained for PRL. Immunostaining for PRL was found in the pituitary tumours from two patients but in neither patient was there a PRL response after oCRH. A GH response was found in 13 of 20 patients in whom it was sought; no patient showed immunostaining in their tumour. GH immunostaining was found in two tumours but in neither patient was there a GH response after oCRH. The oCRH-induced increase of GH and PRL was always recorded in the dominant inferior petrosal sinus. The ACTH response to oCRH was significantly higher in patients who

  3. Prior administration of a non-steroidal anti-androgen failed to prevent the flare-up caused by a luteinizing hormone-releasing hormone agonist in a patient with metastatic prostate cancer.

    Science.gov (United States)

    Uehara, Sho; Yuasa, Takeshi; Fujii, Yasuhisa; Yano, Akihiro; Yamamoto, Shinya; Masuda, Hitoshi; Fukui, Iwao; Yonese, Junji

    2015-08-05

    'Flare phenomenon' after initial luteinizing hormone-releasing hormone agonist administration is a widely approved concept in the treatment of prostate cancer. In most guidelines, concomitant therapy with anti-androgens is recommended to prevent this flare phenomenon. However, there are few reports describing serum prostate-specific antigen transitions after hormonal therapy. Here, we present a case of a man who experienced the biochemical and clinical flare phenomenon despite prior anti-androgen use and who has detailed data. A 70-year-old Asian man with metastatic prostate cancer (multiple bone) was referred to our hospital. He was treated with prior anti-androgens and luteinizing hormone-releasing hormone agonist. Regardless of prior use of anti-androgens, his low back pain caused by bone metastases was deteriorated and serum prostate-specific antigen level was raised from 974.8 ng/mL to 2,555.5 ng/mL within 3 weeks. Then, his serum prostate specific antigen level started to decrease along with the pain. The nadir reached 1.0 ng/mL and remained for 6 months. Because the serum level of prostate-specific antigen then began to increase again, anti-androgen was discontinued for anti-androgen withdrawal syndrome. Then the serum level decreased again to less than 0.1 ng/mL. Until now, his serum prostate-specific antigen level has been maintained at less than 0.1 ng/mL for more than 30 months without any clinical progressions. We present the case of a patient in whom a clinical flare caused by an leuteinizing hormone-releasing hormone agonist was not prevented by prior anti-androgen administration. In addition, the nadir level of prostate-specific antigen when he received leuteinizing hormone-releasing hormone monotherapy was ten times lower than when he received concomitant therapy, and period of anti-androgen withdrawal syndrome was longer than usual. In this case, anti-androgen was probably not effective from the initial administration. Awareness of the possibility

  4. Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting.

    Science.gov (United States)

    Tuziak, Sarah M; Volkoff, Hélène

    2013-12-01

    Melanin-concentrating hormone (MCH) is classically known for its role in regulating teleost fish skin color change for environmental adaptation. Recent evidence suggests that MCH also has appetite-stimulating properties. The gonadotropin-releasing hormone (GnRH) peptide family has dual roles in endocrine control of reproduction and energy status in fish. Atlantic cod (Gadus morhua) are a commercially important aquaculture species inhabiting the shores of Atlantic Canada. In this study, we examine MCH and GnRH transcript expression profiles during early development as well as in central and peripheral tissues and quantify juvenile Atlantic cod MCH and GnRH hypothalamic mRNA expressions following food deprivation. MCH and GnRH3 cDNAs are maternally deposited into cod eggs, while MCH has variable expression throughout early development. GnRH2 and GnRH3 mRNAs "turn-on" during mid-segmentation once the brain is fully developed. For both MCH and GnRH, highest expression appears during the exogenous feeding stages, perhaps supporting their functions as appetite regulators during early development. MCH and GnRH transcripts are found in brain regions related to appetite regulation (telencephalon/preoptic area, optic tectum/thalamus, hypothalamus), as well as the pituitary gland and the stomach, suggesting a peripheral function in food intake regulation. Atlantic cod MCH mRNA is upregulated during fasting, while GnRH2 and GnRH3 transcripts do not appear to be influenced by food deprivation. In conclusion, MCH might be involved in stimulating food intake in juvenile Atlantic cod, while GnRHs may play a more significant role in appetite regulation during early development. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

    Science.gov (United States)

    Lambertini, M; Ceppi, M; Poggio, F; Peccatori, F A; Azim, H A; Ugolini, D; Pronzato, P; Loibl, S; Moore, H C F; Partridge, A H; Bruzzi, P; Del Mastro, L

    2015-12-01

    The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Nicotine self-administration diminishes stress-induced norepinephrine secretion but augments adrenergic-responsiveness in the hypothalamic paraventricular nucleus and enhances adrenocorticotropic hormone and corticosterone release.

    Science.gov (United States)

    Yu, Guoliang; Sharp, Burt M

    2010-03-01

    Chronic nicotine self-administration augments the thalamo-pituitary-adrenal (HPA) responses to stress. Altered neuropeptide expression within corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) contributes to this enhanced HPA response to stress. Herein, we determined the role of norepinephrine, a primary regulator of CRF neurons, in the responses to footshock during nicotine self-administration. On day 12-15 of self-administration, microdialysis showed nicotine reduced PVN norepinephrine release by footshock (nicotine (2-fold) than saline. Additionally, PVN phenylephrine (alpha(1) agonist) stimulated adrenocorticotropic hormone and corticosterone release to a similar extent in unstressed rats self-administering nicotine or saline. Nicotine self-administration also decreased footshock-induced c-Fos expression in the nucleus of the solitary tract-A2/C2 catecholaminergic neurons that project to the PVN. Therefore, footshock-induced nucleus of the solitary tract activation and PVN norepinephrine input are both attenuated by nicotine self-administration, yet PVN CRF neurons are more responsive to alpha(1) stimulation, but only during stress. This plasticity in noradrenergic regulation of PVN CRF neurons provides a new mechanism contributing to the HPA sensitization to stress by nicotine self-administration and smoking.

  7. Growth hormone-releasing peptide ghrelin inhibits homocysteine-induced endothelial dysfunction in porcine coronary arteries and human endothelial cells.

    Science.gov (United States)

    Hedayati, Nasim; Annambhotla, Suman; Jiang, Jun; Wang, Xinwen; Chai, Hong; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Ghrelin, a novel growth hormone-releasing peptide, is implicated to play a protective role in cardiovascular tissues. However, it is not clear whether ghrelin protects vascular tissues from injury secondary to risk factors such as homocysteine (Hcy). This study investigated the effect and potential mechanisms of ghrelin on Hcy-induced endothelial dysfunction. Porcine coronary artery rings were incubated for 24 hours with ghrelin (100 ng/mL), Hcy (50 microM), or ghrelin plus Hcy. Endothelial vasomotor function was evaluated using the myograph tension model. The response to the thromboxane A(2)analog U46619, bradykinin, and sodium nitroprusside was analyzed. Endothelial nitric oxide synthase (eNOS) expression was determined using real-time polymerase chain reaction and immunohistochemistry staining, and superoxide anion production was documented lucigenin-enhanced chemiluminescence analysis. Human coronary artery endothelial cells (HCAECs) were treated with different concentrations of Hcy, ghrelin, or antighrelin receptor antibody for 24 hours, and eNOS protein levels were determined by Western blot analysis. Maximal contraction with U46619 and endothelium-independent vasorelaxation with sodium nitroprusside were not different among the four groups. However, endothelium-dependent vasorelaxation with bradykinin (10(-6) M) was significantly reduced by 34% with Hcy compared with controls (P ghrelin to Hcy had a protective effect, with 61.6% relaxation, which was similar to controls (64.7%). Homocysteine significantly reduced eNOS expression, whereas ghrelin cotreatment effectively restored eNOS expression to the control levels. Superoxide anion levels, which were increased by 100% with Hcy, returned to control levels with ghrelin cotreatment. Ghrelin also effectively blocked the Hcy-induced decrease of eNOS protein levels in HCAECs in a concentration-dependent manner. Antighrelin receptor antibody effectively inhibited the effect of ghrelin. Ghrelin has a protective

  8. Neuronal Gonadotrophin-Releasing Hormone (GnRH) and Astrocytic Gonadotrophin Inhibitory Hormone (GnIH) Immunoreactivity in the Adult Rat Hippocampus.

    Science.gov (United States)

    Ferris, J K; Tse, M T; Hamson, D K; Taves, M D; Ma, C; McGuire, N; Arckens, L; Bentley, G E; Galea, L A M; Floresco, S B; Soma, K K

    2015-10-01

    Gonadotrophin-releasing hormone (GnRH) and gonadotrophin inhibitory hormone (GnIH) are neuropeptides secreted by the hypothalamus that regulate reproduction. GnRH receptors are not only present in the anterior pituitary, but also are abundantly expressed in the hippocampus of rats, suggesting that GnRH regulates hippocampal function. GnIH inhibits pituitary gonadotrophin secretion and is also expressed in the hippocampus of a songbird; its role outside of the reproductive axis is not well established. In the present study, we employed immunohistochemistry to examine three forms of GnRH [mammalian GnRH-I (mGnRH-I), chicken GnRH-II (cGnRH-II) and lamprey GnRH-III (lGnRH-III)] and GnIH in the adult rat hippocampus. No mGnRH-I and cGnRH-II+ cell bodies were present in the hippocampus. Sparse mGnRH-I and cGnRH-II+ fibres were present within the CA1 and CA3 fields of the hippocampus, along the hippocampal fissure, and within the hilus of the dentate gyrus. No lGnRH-III was present in the rodent hippocampus. GnIH-immunoreactivity was present in the hippocampus in cell bodies that resembled astrocytes. Males had more GnIH+ cells in the hilus of the dentate gyrus than females. To confirm the GnIH+ cell body phenotype, we performed double-label immunofluorescence against GnIH, glial fibrillary acidic protein (GFAP) and NeuN. Immunofluorescence revealed that all GnIH+ cell bodies in the hippocampus also contained GFAP, a marker of astrocytes. Taken together, these data suggest that GnRH does not reach GnRH receptors in the rat hippocampus primarily via synaptic release. By contrast, GnIH might be synthesised locally in the rat hippocampus by astrocytes. These data shed light on the sites of action and possible functions of GnRH and GnIH outside of the hypothalamic-pituitary-gonadal axis. © 2015 British Society for Neuroendocrinology.

  9. Prognostic factors for survival in metastatic breast cancer by hormone receptor status

    NARCIS (Netherlands)

    Kwast, A.B.G.; Voogd, A.C.; Menke-Pluijmers, M.B.E.; Linn, S.C.; Sonke, G.S.; Kiemeney, L.A.; Siesling, Sabine

    2014-01-01

    Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when

  10. Diverse effects of tachykinins on luteinizing hormone release in male rats: mechanism of action.

    Science.gov (United States)

    Kalra, P S; Sahu, A; Bonavera, J J; Kalra, S P

    1992-09-01

    The tachykinins are a group of structurally related peptides found in the rat hypothalamus and anterior pituitary. We have evaluated the effects of four tachykinins on LH release in male rats. In intact male rats, intracerebroventricular (icv) injection of neurokinin A (NKA), neuropeptide K (NPK), and neuropeptide-gamma (NP gamma) elicited dose-related, transient increases in plasma LH. Substance P (SP) was ineffective under these conditions. A further examination showed that in vitro incubation with either NPK or NP gamma of hemipituitaries from intact but not castrated male rats promoted release of LH into the medium, thereby revealing that the excitatory effects of tachykinins in intact male rats may, in part, be a result of stimulation of LH release directly from the anterior pituitary. On the other hand, the effects of these four tachykinins on LH release were different in castrated rats. Intracerebroventricular injection of NPK, NKA, and NP gamma as well as SP, which was ineffective in intact male rats, evoked a long-lasting suppression of LH release. Comparatively, NPK was the most effective tachykinin in eliciting LH responses in both of these tests involving different endocrine environments. We next evaluated the possibility that the inhibitory effects of tachykinins (NPK) may be mediated by activation of inhibitory endogenous opioid peptides. The results showed that iv infusion of the opiate receptor antagonist naloxone, to block the possible inhibitory effects of endogenous opioid peptides, only partially counteracted the suppressive effects of icv NPK on plasma LH levels. Thus, in addition to revealing the diverse effects of structurally related tachykinins on LH release, the results of these investigations showed specifically that the NK-2 receptor agonists NPK, NP gamma, and NKA stimulated LH release in intact rats, in part, by a direct action at the level of the pituitary, whereas the NK-1 receptor agonist SP was inactive under these conditions

  11. Differential expression of three types of gonadotropin-releasing hormone genes during the spawning season in grass puffer, Takifugu niphobles.

    Science.gov (United States)

    Shahjahan, Md; Hamabata, Tomoko; Motohashi, Eiji; Doi, Hiroyuki; Ando, Hironori

    2010-05-15

    Grass puffer, Takifugu niphobles, has unique spawning behavior; spawning occurs on beach only for several days around new moon and full moon from spring to early summer. To investigate the role of gonadotropin-releasing hormone (GnRH) in the reproductive function, genes encoding three types of GnRHs, namely seabream GnRH (sbGnRH), chicken GnRH-II (cGnRH-II) and salmon GnRH (sGnRH), were cloned and changes in their mRNA amounts were examined over the spawning season. In addition, changes in the pituitary gonadotropin subunit mRNAs and the plasma steroid hormones were examined over the spawning season. Fishes were assessed at four reproductive stages, i.e., in December (early maturation), in April (maturing), in May (spawning), and in July (post-spawning). Moreover, spawning fish just after releasing eggs and sperm were taken at a spawning bed. The amounts of sbGnRH mRNA were substantially elevated in May and the spawning fish in both sexes, concomitant with considerable elevations of follicle-stimulating hormone and luteinizing hormone beta subunit mRNAs and plasma estradiol-17beta (E(2)) and testosterone (T) levels. There were strong positive correlations between the sbGnRH mRNA and the plasma E(2) and T levels over the spawning season in both sexes. The amounts of cGnRH-II mRNA showed no noticeable changes except for an increase in the post-spawning females. The amounts of sGnRH mRNA in the males were significantly increased in May, but they were low in the spawning males. In the females, sGnRH mRNA increased from the maturing stage and reached a maximum in the post-spawning stage, in which a positive correlation with the plasma cortisol levels was observed. These specific changes suggest that the expression of three types of GnRH genes is differentially regulated during the spawning season, and sex steroids may be important for the differential expression of GnRH genes. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Restraint stress increases serotonin release in the central nucleus of the amygdala via activation of corticotropin-releasing factor receptors.

    Science.gov (United States)

    Mo, Bing; Feng, Na; Renner, Kenneth; Forster, Gina

    2008-07-30

    Decreases in serotonergic activity in the central nucleus of the amygdala reduce responses to stressors, suggesting an important role for serotonin in this region of the amygdala in stress reactivity. However, it is not known whether exposure to stressors actually increases serotonin release in the central nucleus of the amygdala. The current experiment tested the hypothesis that restraint stress increases extracellular serotonin within the central nucleus of the amygdala and adjacent medial amygdala using in vivo microdialysis in awake male rats during the dark phase of the light-dark cycle. Serotonin release in the central nucleus increased immediately in response to restraint stress. In contrast, there was no change in serotonin release within the adjacent medial amygdala during or following restraint. Since corticotropin-releasing factor is an important mediator of both responses to stressors and serotonergic activity, subsequent experiments tested the hypothesis that central nucleus serotonergic response to restraint stress is mediated by central corticotropin-releasing factor receptors. Administration of the corticotropin-releasing factor type 1 and 2 receptor antagonist d-Phe-CRF (icv, 10 microg/5 microl) prior to restraint stress suppressed restraint-induced serotonin release in the central nucleus. The results suggest that restraint stress rapidly and selectively increases serotonin release in the central nucleus of the amygdala by the activation of central corticotropin-releasing factor receptors. Furthermore, the results imply that corticotropin-releasing factor mediated serotonergic activity in central nucleus of the amygdala may be an important component of a stress response.

  13. Controlled growth factor release from synthetic extracellular matrices

    Science.gov (United States)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  14. Bed rest suppresses bioassayable growth hormone release in response to muscle activity

    Science.gov (United States)

    McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

    1997-01-01

    Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P muscle activity.

  15. Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

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    Dayanidhi Jena

    2016-10-01

    Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

  16. Ovarian response to pregnant mare serum gonadotropin and porcine pituitary extract in gilts actively immunized against gonadotropin releasing hormone.

    Science.gov (United States)

    Esbenshade, K L

    1987-12-01

    Two experiments were conducted to determine the effect of exogenous gonadotropins on follicular development in gilts actively immunized against gonadotropin releasing hormone (GnRH). Four gilts, which had become acyclic after immunization against GnRH, and four control gilts were given 1,000 IU pregnant mare serum gonadotropin (PMSG), while four additional control gilts were given saline. Control animals were prepuberal crossbred gilts averaging 100 kg body weight. Control gilts given saline had ovaries containing antral follicles (4 to 6 mm in diameter). Control gilts given PMSG exhibited estrus and their ovaries contained corpora hemorrhagica and corpora lutea. PMSG failed to stimulate follicular growth in gilts immunized against GnRH, and ovaries contained regressed corpora albicantia and small antral follicles (less than 1 mm in diameter). Concentrations of luteinizing hormone (LH) and estradiol-17 beta (E2) were non-detectable in gilts immunized against GnRH and given PMSG. In the second experiment, five gilts actively immunized against GnRH were given increasing doses of PMSG every third day until unilateral ovariectomy on d 50. PMSG failed to stimulate follicular growth, and concentrations of follicle stimulating hormone (FSH), E2 and LH were not detectable. Six weeks later, gilts were given a booster immunization and then were given 112 micrograms LH and 15 micrograms FSH intravenously every 6 h for 9 d. The remaining ovary was removed on d 10. Although LH and FSH concentrations were elevated, administration of gonadotropins did not stimulate follicular growth or increase E2 concentrations. These results indicate that neither PMSG or exogenous LH and FSH can induce E2 synthesis or sustain follicular development in gilts actively immunized against GnRH.

  17. Liver X receptor regulation of thyrotropin-releasing hormone transcription in mouse hypothalamus is dependent on thyroid status.

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    Rym Ghaddab-Zroud

    Full Text Available Reversing the escalating rate of obesity requires increased knowledge of the molecular mechanisms controlling energy balance. Liver X receptors (LXRs and thyroid hormone receptors (TRs are key physiological regulators of energetic metabolism. Analysing interactions between these receptors in the periphery has led to a better understanding of the mechanisms involved in metabolic diseases. However, no data is available on such interactions in the brain. We tested the hypothesis that hypothalamic LXR/TR interactions could co-regulate signalling pathways involved in the central regulation of metabolism. Using in vivo gene transfer we show that LXR activation by its synthetic agonist GW3965 represses the transcriptional activity of two key metabolic genes, Thyrotropin-releasing hormone (Trh and Melanocortin receptor type 4 (Mc4r in the hypothalamus of euthyroid mice. Interestingly, this repression did not occur in hypothyroid mice but was restored in the case of Trh by thyroid hormone (TH treatment, highlighting the role of the triiodothyronine (T3 and TRs in this dialogue. Using shLXR to knock-down LXRs in vivo in euthyroid newborn mice, not only abrogated Trh repression but actually increased Trh transcription, revealing a potential inhibitory effect of LXR on the Hypothalamic-Pituitary-Thyroid axis. In vivo chromatin immunoprecipitation (ChIP revealed LXR to be present on the Trh promoter region in the presence of T3 and that Retinoid X Receptor (RXR, a heterodimerization partner for both TR and LXR, was never recruited simultaneously with LXR. Interactions between the TR and LXR pathways were confirmed by qPCR experiments. T3 treatment of newborn mice induced hypothalamic expression of certain key LXR target genes implicated in metabolism and inflammation. Taken together the results indicate that the crosstalk between LXR and TR signalling in the hypothalamus centres on metabolic and inflammatory pathways.

  18. The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation

    DEFF Research Database (Denmark)

    Kol, Shahar; Homburg, Roy; Alsbjerg, Birgit

    2012-01-01

    Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-releasing...... hormone antagonist protocol should be the protocol of choice for the PCOS patient undergoing ovarian stimulation with gonadotropins for in vitro fertilization. If an excessive ovarian response is encountered, the clinician will always have two options: either to trigger final oocyte maturation...

  19. Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys

    DEFF Research Database (Denmark)

    Christiansen, P; Müller, J; Buhl, S

    1988-01-01

    We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled...... the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p...... = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0...

  20. Afferent neuronal control of type-I gonadotropin releasing hormone (GnRH neurons in the human

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    Erik eHrabovszky

    2013-09-01

    Full Text Available Understanding the regulation of the human menstrual cycle represents an important ultimate challenge of reproductive neuroendocrine research. However, direct translation of information from laboratory animal experiments to the human is often complicated by strikingly different and unique reproductive strategies and central regulatory mechanisms that can be present in even closely related animal species. In all mammals studied so far, type-I gonadotropin releasing hormone (GnRH synthesizing neurons form the final common output way from the hypothalamus in the neuroendocrine control of the adenohypophysis. Under various physiological and pathological conditions, hormonal and metabolic signals either regulate GnRH neurons directly or act on upstream neuronal circuitries to influence the pattern of pulsatile GnRH secretion into the hypophysial portal circulation. Neuronal afferents to GnRH cells convey important metabolic-, stress-, sex steroid-, lactational- and circadian signals to the reproductive axis, among other effects. This article gives an overview of the available neuroanatomical literature that described the afferent regulation of human GnRH neurons by peptidergic, monoaminergic and amino acidergic neuronal systems. Recent studies of human genetics provided evidence that central peptidergic signaling by kisspeptins and neurokinin B play particularly important roles in puberty onset and later, in the sex steroid-dependent feedback regulation of GnRH neurons. This review article places special emphasis on the topographic distribution, sexual dimorphism, aging-dependent neuroanatomical changes and plastic connectivity to GnRH neurons of the critically important human hypothalamic kisspeptin and neurokinin B systems.

  1. Diacylglycerol acyltransferase-1 (DGAT1 inhibition perturbs postprandial gut hormone release.

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    Hua V Lin

    Full Text Available Diacylglycerol acyltransferase-1 (DGAT1 is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1 and peptide YY (PYY only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4 inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

  2. [Clinical efficacy and safety of gonadotropin releasing hormone agonist combined with estrogen-dydrogesteronea in treatment of endometriosis].

    Science.gov (United States)

    Long, Qi-qi; Zhang, Shao-fen; Han, Yi; Chen, Hang; Li, Xue-lian; Hua, Ke-qin; Hu, Wei-guo

    2010-04-01

    To compare clinical effect of gonadotropin releasing hormone agonist (GnRH-a) alone and GnRH-a combined with low-dose dydrogesteronea and estradiol valerate on sex hormone, hypoestrogenic symptoms, quality of life and bone mineral density (BMD) in treatment of endometriosis. Seventy patients with moderate or severe endometriosis, who were diagnosed by laparotomy or laparoscopic surgery within two months, were randomly assigned into two groups. 35 patients in GnRH-a group were treated by goserelin (3.6 mg) for three months, and 35 patients in add-back group were treated by goserelin (3.6 mg) combined with estradiol valerate 0.5 mg and dydrogesteronea 5 mg daily. Before and after the treatment, clinical parameters were recorded and analyzed, including visual analog scale (VAS), medical outcomes survey short form 36 (SF-36), Kupperman menopausal index (KMI), BMD, the serum level of follicle stimulating hormone (FSH), estradiol (E2) and bone gla-protein (BGP). The first menstruation and VAS were also followed up after treatment. Every 3 cases in two groups lost follow-up. (1) Reproductive hormone: the level of E2 in add-back group [(94+/-71) pmol/L] was significantly higher than (54+/-52) pmol/L in GnRH-a group (PKMI: KMI in add back-group (10+/-8)was significantly lower than (14+/-6) in GnRH-a group (P<0.05). (4) BMD: compared with that before treatment, BMD decreased significantly after treatment in GnRH-a group (P<0.05), no remarkable difference of BMD was observed before and after treatment in add-back group. Before treatment, serum BGP in both groups did not show statistical difference. After treatment, the level of BGP in GnRH-a group [(7932+/-5206) ng/L] was significantly higher than (5419+/-2917) ng/L in add-back group (P<0.05). GnRH-a combined with estrogen-progesterone regimen could relieve pain from endometriosis as effectively as GnRH-a alone and reduce hypoestrogenic symptoms and bone loss. Therefore, it is a safe and effective treatment.

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

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    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.

  4. Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

    Science.gov (United States)

    Zhou, Wen; Håkansson, Kristina

    2013-11-01

    Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

  5. Photoperiod-dependent regulation of gonadotropin-releasing hormone 1 messenger ribonucleic acid levels in the songbird brain.

    Science.gov (United States)

    Stevenson, Tyler J; Bernard, Daniel J; McCarthy, Margaret M; Ball, Gregory F

    2013-09-01

    Annual changes in day length induce marked changes in reproductive function in temperate zone vertebrates. In many avian species, in contrast to other seasonally breeding animals, plasticity in hypothalamic gonadotropin-releasing hormone - 1 (GnRH1) expression rather than (or in addition to) release governs changes in pituitary-gonadal activity. Investigations of the cellular and molecular mechanisms that govern GnRH1 plasticity were previously hindered by a collective inability of scientists in the field to characterize the gnrh1 cDNA in songbirds. We finally overcame this roadblock after data from the zebra finch (Taeniopygia guttata) genome project enabled us to rapidly clone the gnrh1 cDNA from hypothalamic RNA of zebra finches and European starlings (Sturnus vulgaris). Here, we review the original data that identified GnRH1 protein plasticity in the songbird brain and discuss earlier failed attempts to clone gnrh1 in these animals. Then, we present recent efforts, including our own, that successfully characterized gnrh1 in zebra finch and starling, and demonstrated dynamic regulation of gnrh1 mRNA expression, particularly in sub-populations of preoptic area neurons, in the latter. Overall, this paper highlights GnRH1 plasticity in the avian brain, and weaves into the narrative the previously untold story of the challenges to sequencing gnrh1 in songbirds. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion.

  7. Testosterone production in response to exogenous gonadotropin releasing hormone (GnRH challenge) depends on social environment and color polymorphism.

    Science.gov (United States)

    Cain, Kristal E; Pryke, Sarah R

    2017-04-01

    Testosterone is an important mediator of behavior, morphology and physiology. A cascade of signals regulates the amount of testosterone (T) circulating in the plasma; in response to stimulus the hypothalamus releases gonadotropin-releasing hormone (GnRH), which triggers secretion of gonadotropins from the pituitary, stimulating the synthesis and release of T from the gonads. Previous work has shown that changes to the social environment can alter circulating T-levels, which may have important fitness consequences, but it is currently unclear whether these changes are due to alterations in the signal from the brain, or changes in the ability of the pituitary and gonads to respond to this signal. Further, the strength and direction of response to a changing environment may differ according to life-history strategy. Species with genetically determined alternative strategies offer a pathway for examining these differences. Here we use a finch with a genetically determined polymorphism, the Gouldian finch (Erythrura gouldiae), to determine whether T-levels change in response to social environment. We also use injections of GnRH to determine whether these changes are due to alterations in the ability of the pituitary and gonads to respond to this signal. We found that social environment (presence of females) had a rapid effect on male circulating T-levels, and that this difference was reflected in responsiveness to GnRH. We observed no overall morph differences in T-levels, but we did observe morph differences in the pattern of T secretion across environments, and morph differences in the repeatability of T-levels across time and environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Role of gonadotrophin releasing hormone baseline concentrations in the control of pituitary gonadotrophin and ovarian steroid secretion in the pseudopregnant rat

    NARCIS (Netherlands)

    Schuiling, GA; Valkhof, N; Koiter, TR

    To study the effect of moderately elevated gonadotrophin releasing hormone (GnRH) baseline concentrations during the luteal and the follicular phase, pseudopregnant rats were infused s.c. with GnRH at several doses for 5 days, These rats were also treated with oestradiol or sham-treated during the

  9. In-vitro/in-vivo studies of the biodegradable poly-(D,L-lactide-co-glycolide) microspheres of a novel luteinizing hormone-releasing hormone antagonist for prostate cancer treatment.

    Science.gov (United States)

    Du, Lina; Mei, Xingguo; Wang, Chenyun; Li, Xin; Zhang, Fucheng; Jin, Yiguang

    2011-03-01

    The introduction of luteinizing hormone-releasing hormone (LHRH) analogs and their antagonists is revolutionizing the treatment of prostate cancer. In this study, poly(D,L-lactideco-glycolide) (PLGA) microspheres containing a highly potent LHRH antagonist (LXT-101) of interest in the indication of prostate cancer were evaluated on release mechanisms in vitro and biological performance in vivo. LXT-101 microspheres were prepared by the water/oil/water double emulsion method and the solid/oil/oil method. The results showed that the mechanism of LXT-101 releasing from PLGA 14,000 microspheres was the cooperation of drug diffusion and polymer degradation. This clarified the relationship between the microsphere characterization and hormone level in vivo. The larger microspheres (33 μm) could inhibit the testosterone level to castration for a longer time (35 days) than the smaller microspheres (15 μm, 14 days). The formulation containing the hydrophilic additive (polyethylene glycol 6000) could suppress the testosterone level to castration for a longer time (> 35 days) than the formulation without polyethylene glycol (14 days). The appearance of testis, vesicular seminalis, and prostates changed after treatment. The weights of sexual organs decreased significantly. The in-vivo release of the LXT-101 PLGA 14,000 microspheres curve showed that in-vivo release started immediately after day 1 (22.7%) and was rapid during the first 5 days (40.2% release). The LXT-101 microspheres could be a promising drug delivery system candidate to treat sex hormone-dependent tumors and other related disorders.

  10. Two complementary methods to control gonadotropin-releasing hormone vaccination (Improvac®) misuse in horseracing: Enzyme-linked immunosorbent assay test in plasma and steroidomics in urine.

    Science.gov (United States)

    Bailly-Chouriberry, Ludovic; Loup, Benoit; Popot, Marie-Agnès; Dreau, Marie-Laure; Garcia, Patrice; Bruyas, Jean-François; Bonnaire, Yves

    2017-09-01

    Since the availability on the European market of the vaccine Improvac® dedicated to male pig immunological castration, the risk of misuse of this product in horses is now considered as a threat for the horseracing industry. Immunological castration is not allowed by the racing codes (immune system, Article 6). Indeed, this vaccination against the hypothalamic hormone luteinizing hormone-releasing hormone or gonadotropin-releasing hormone (GnRH) will prevent the release from the anterior pituitary of luteinizing hormone and follicle stimulating hormone, which are required for the development and activity of gonads in males (testes) and female (ovaries) and therefore all their subsequent physiological functions. This treatment will induce a strong hormonal variation resulting in a behaviour modification of the animals. In this work, four male standardbreds treated with Improvac® vaccine (two intramuscular injections within 4 weeks) were studied. Monitoring of the total scrotal width showed a decrease of the scrotum size (37%) and production of anti-GnRH antibodies was detected up to 200 days after the first injection. Anti-GnRH antibodies were detected in plasma after caprylic acid precipitation followed by an enzyme-linked immunosorbent assay (ELISA) as a rapid and efficient screening method applicable to routine analysis. These results were correlated to a switch of the sexual status from male group to gelding/female group obtained by a steroidomic approach with urine based on ten endogenous compounds. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Growth Hormone–Releasing Hormone Effects on Brain γ-Aminobutyric Acid Levels in Mild Cognitive Impairment and Healthy Aging

    Science.gov (United States)

    Friedman, Seth D.; Baker, Laura D.; Borson, Soo; Jensen, J. Eric; Barsness, Suzanne M.; Craft, Suzanne; Merriam, George R.; Otto, Randolph K.; Novotny, Edward J.; Vitiello, Michael V.

    2013-01-01

    Importance Growth hormone–releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response. Objective To examine the neurochemical effects of GHRH in a subset of participants from the parent trial. Design Randomized, double-blind, placebo-controlled substudy of a larger trial. Setting Clinical research unit at the University of Washington School of Medicine. Participants Thirty adults (17 with mild cognitive impairment [MCI]), ranging in age from 55 to 87 years, were enrolled and successfully completed the study. Interventions Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analogue of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline and weeks 10 and 20, participants underwent brain magnetic resonance imaging and spectroscopy protocols and cognitive testing and provided blood samples after fasting. Participants also underwent glucose tolerance tests before and after intervention. Main Outcomes and Measures Brain levels of glutamate, inhibitory transmitters γ-aminobutyric acid (GABA) and N-acetylaspartylglutamate (NAAG), and myo-inositol (MI), an osmolyte linked to Alzheimer disease in humans, were measured in three 2×2×2-cm3 left-sided brain regions (dorsolateral frontal, posterior cingulate, and posterior parietal). Glutamate, GABA, and MI levels were expressed as ratios to creatine plus phospho-creatine, and NAAG was expressed as a ratio to N-acetylaspartate. Results After 20 weeks of GHRH administration, GABA levels were increased in all brain regions (P<.04), NAAG levels were increased (P=.03) in the dorsolateral frontal cortex, and MI levels were decreased in the posterior cingulate (P=.002). These effects were similar in adults with MCI and older adults with normal cognitive function. No changes in

  12. Regulatory Architecture of the LβT2 Gonadotrope Cell Underlying the Response to Gonadotropin-Releasing Hormone

    Directory of Open Access Journals (Sweden)

    Frederique Ruf-Zamojski

    2018-02-01

    Full Text Available The LβT2 mouse pituitary cell line has many characteristics of a mature gonadotrope and is a widely used model system for studying the developmental processes and the response to gonadotropin-releasing hormone (GnRH. The global epigenetic landscape, which contributes to cell-specific gene regulatory mechanisms, and the single-cell transcriptome response variation of LβT2 cells have not been previously investigated. Here, we integrate the transcriptome and genome-wide chromatin accessibility state of LβT2 cells during GnRH stimulation. In addition, we examine cell-to-cell variability in the transcriptional response to GnRH using Gel bead-in-Emulsion Drop-seq technology. Analysis of a bulk RNA-seq data set obtained 45 min after exposure to either GnRH or vehicle identified 112 transcripts that were regulated >4-fold by GnRH (FDR < 0.05. The top regulated transcripts constitute, as determined by Bayesian massive public data integration analysis, a human pituitary-relevant coordinated gene program. Chromatin accessibility [assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq] data sets generated from GnRH-treated LβT2 cells identified more than 58,000 open chromatin regions, some containing notches consistent with bound transcription factor footprints. The study of the most prominent open regions showed that 75% were in transcriptionally active promoters or introns, supporting their involvement in active transcription. Lhb, Cga, and Egr1 showed significantly open chromatin over their promoters. While Fshb was closed over its promoter, several discrete significantly open regions were found at −40 to −90 kb, which may represent novel upstream enhancers. Chromatin accessibility determined by ATAC-seq was associated with high levels of gene expression determined by RNA-seq. We obtained high-quality single-cell Gel bead-in-Emulsion Drop-seq transcriptome data, with an average of >4,000 expressed genes

  13. Impact of sex hormones, insulin, growth factors and peptides on cartilage health and disease.

    Science.gov (United States)

    Claassen, Horst; Schicht, Martin; Paulsen, Friedrich

    2011-02-01

    Sex hormones contribute to the pathogenesis of osteoarthritis (OA) in both sexes. OA is normally not seen in pre-menopausal women, whereas men may develop the disease as early as the 30th year of life. OA also shows increased incidence in association with diseases such as diabetes mellitus. Recent years have seen characterization of essential components of a functional endocrinal network in the articular cartilage comprising not only sex hormones but apparently insulin, growth factors and various peptides as well. In this review, we summarize the latest information regarding the influence of sex hormones, insulin, growth factors and some peptides on healthy cartilage and their involvement in osteoarthritis. Both animal and human research data were considered. The results are presented in an information matrix that identifies what is known, with supporting references, and identifies areas for further investigation. Copyright © 2010 Elsevier GmbH. All rights reserved.

  14. Impact of sex and gender on corticotropin releasing factor and noradrenergic sensitivity in cocaine use disorder

    Science.gov (United States)

    McRae-Clark, Aimee L.; Cason, Angie M.; Kohtz, Amy S.; Maria, Megan Moran-Santa; Aston-Jones, Gary; Brady, Kathleen T.

    2016-01-01

    Responses to stress may be important in understanding sex and gender differences in substance use disorders and may also be a target for development of treatment interventions. A growing body of both preclinical and clinical research supports important underlying sex and gender differences in the corticotropin releasing factor (CRF) and noradrenergic systems, which may contribute to drug use. Preclinical models have demonstrated increased sensitivity of females as compared to males to CRF and noradrenergic-induced drug reinstatement, and, consistent with these findings, human laboratory studies have demonstrated greater sensitivity to corticotropin releasing hormone (CRH) and noradrenergic stimulation in cocaine-dependent women as compared to men. Further, neuroimaging studies have demonstrated increased neural response to stressful stimuli in cocaine-dependent women as compared to men, as well as shown significant sex differences in the sensitivity of brain regions responsible for regulating response to CRH. Development of interventions targeting the noradrenergic system and stress response in drug-dependent individuals could have important clinical implications for both women and men. PMID:27870396

  15. Impact of gender on corticotropin-releasing factor and noradrenergic sensitivity in cocaine use disorder.

    Science.gov (United States)

    McRae-Clark, Aimee L; Cason, Angie M; Kohtz, Amy S; Moran Santa-Maria, Megan; Aston-Jones, Gary; Brady, Kathleen T

    2017-01-02

    Responses to stress may be important in understanding gender differences in substance use disorders and may also be a target for development of treatment interventions. A growing body of both preclinical and clinical research supports important underlying gender differences in the corticotropin-releasing factor (CRF) and noradrenergic systems, which may contribute to drug use. Preclinical models have demonstrated increased sensitivity of females to CRF and noradrenergic-induced drug reinstatement compared with males, and, consistent with these findings, human laboratory studies have demonstrated greater sensitivity to corticotropin-releasing hormone (CRH) and noradrenergic stimulation in cocaine-dependent women compared with men. Furthermore, neuroimaging studies have demonstrated increased neural response to stressful stimuli in cocaine-dependent women compared with men as well as showing significant sex differences in the sensitivity of brain regions responsible for regulating the response to CRH. Development of interventions targeting the noradrenergic system and stress response in drug-dependent individuals could have important clinical implications for both women and men. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Impact of gonadotropin-releasing hormone antagonist addition on pregnancy rates in gonadotropin-stimulated intrauterine insemination cycles

    Directory of Open Access Journals (Sweden)

    Shikha Jain

    2016-01-01

    Full Text Available OBJECTIVES: The objective of the study is to evaluate the efficacy of gonadotropin-releasing hormone (GnRH antagonist in improving clinical pregnancy rate in gonadotropin-stimulated intrauterine insemination (IUI cycles in patients of unexplained infertility. STUDY DESIGN: This was a prospective, randomized case-controlled study. SETTINGS: The study was conducted in the infertility clinic of a tertiary care center. MATERIALS AND METHODS: Four hundred twenty-seven women undergoing IUI following controlled ovarian stimulation with gonadotropins (recombinant follicle-stimulating hormone [r-FSH] 75 IU/day were randomly divided into two groups. Women in Group I received GnRH antagonist (Cetrorelix 0.25 mg/day in a multiple dose flexible protocol. Women in Group II received r-FSH alone. Ovulatory trigger was given with human chorionic gonadotropin 5000 IU when dominant follicle was ≥18 mm. IUI was performed within 44-48 h. Both groups received similar luteal phase support. Primary outcome measure was clinical pregnancy rate. The trial was powered to detect an absolute increase in clinical pregnancy rate by 13% from an assumed 20% clinical pregnancy rate in the control group, with an alpha error level of 0.05 and a beta error level of 0.20. RESULTS: Clinical pregnancy rate in Groups I and II was 27.6% (n = 56 and 26.5% (n = 54, respectively (P=0.800. Ongoing pregnancy and multiple pregnancy rates were likewise similar between the groups. CONCLUSIONS: Addition of GnRH antagonist to gonadotropin-stimulated IUI cycles results in no significant difference in clinical pregnancy rate.

  17. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

    1999-11-01

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  18. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

    Science.gov (United States)

    Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

    2013-12-01

    The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright

  19. [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation].

    Science.gov (United States)

    Liu, Chang-Qing; Qin, Zi-Xin; Jiang, Fang-Fang; Hong, Ting; Wang, Feng

    2014-11-01

    To observe the effect of Kuntai Capsule (KC), a Chinese patent medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a) treatment for moderate-severe endometriosis (EM). Totally 100 patients suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B), 50 in each group. Patients in Group A were hypodermically injected with goserelin (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each time, three times per day. The therapeutic course for all was 12 weeks. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma-carboxyglutamic-acid-containing proteins (BGP) were measured respectively. Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar vertebra were also compared between the two groups. Serum levels of E2 and FSH both significantly decreased in the two groups at week 12 of the treatment (P KMI increased in the two groups (P 0.05). Serum BGP increased after 12-week treatment (P KMI between the two groups (P > 0.05). As for the incidence of menopausal symptoms, better effects in improving symptoms such as hot flashes, sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P < 0.05). There was no significant difference in the post-pre-treatment difference of BMI between the two groups, but with statistical post-pre-treatment difference in the BGP level (P < 0.05). HKC combined GnRH-a could effectively reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased serum BGP levels after GnRH-a therapy.

  20. 60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary-thyroid axis.

    Science.gov (United States)

    Joseph-Bravo, Patricia; Jaimes-Hoy, Lorraine; Uribe, Rosa-María; Charli, Jean-Louis

    2015-08-01

    This review presents the findings that led to the discovery of TRH and the understanding of the central mechanisms which control hypothalamus-pituitary-thyroid axis (HPT) activity. The earliest studies on thyroid physiology are now dated a century ago when basal metabolic rate was associated with thyroid status. It took over 50 years to identify the key elements involved in the HPT axis. Thyroid hormones (TH: T4 and T3) were characterized first, followed by the semi-purification of TSH whose later characterization paralleled that of TRH. Studies on the effects of TH became possible with the availability of synthetic hormones. DNA recombinant techniques facilitated the identification of all the elements involved in the HPT axis, including their mode of regulation. Hypophysiotropic TRH neurons, which control the pituitary-thyroid axis, were identified among other hypothalamic neurons which express TRH. Three different deiodinases were recognized in various tissues, as well as their involvement in cell-specific modulation of T3 concentration. The role of tanycytes in setting TRH levels due to the activity of deiodinase type 2 and the TRH-degrading ectoenzyme was unraveled. TH-feedback effects occur at different levels, including TRH and TSH synthesis and release, deiodinase activity, pituitary TRH-receptor and TRH degradation. The activity of TRH neurons is regulated by nutritional status through neurons of the arcuate nucleus, which sense metabolic signals such as circulating leptin levels. Trh expression and the HPT axis are activated by energy demanding situations, such as cold and exercise, whereas it is inhibited by negative energy balance situations such as fasting, inflammation or chronic stress. New approaches are being used to understand the activity of TRHergic neurons within metabolic circuits. © 2015 Society for Endocrinology.

  1. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2017-02-01

    Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

  2. Kisspeptin/Gpr54-independent gonadotrophin-releasing hormone activity in Kiss1 and Gpr54 mutant mice.

    Science.gov (United States)

    Chan, Y M; Broder-Fingert, S; Wong, K M; Seminara, S B

    2009-12-01

    The kisspeptin/Gpr54 signalling pathway plays a critical role in reproduction by stimulating the secretion of gonadotrophin-releasing hormone (GnRH), yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For example, a proportion of female Kiss1(-/-) and Gpr54(-/-) mice exhibit vaginal oestrus, and some male Kiss1(-/-) and Gpr54(-/-) mice exhibit spermatogenesis. To characterise this partial sexual maturation, we examined the vaginal cytology of female Kiss1(-/-) and Gpr54(-/-) mice over time. Almost all mutant mice eventually enter oestrus, and then spontaneously transition from oestrus to dioestrus and back to oestrus again. These transitions are not associated with ovulation, and the frequency of these transitions increases with age. The oestrus exhibited by female Kiss1(-/-) and Gpr54(-/-) mice was disrupted by the administration of the competitive GnRH antagonist acyline, which also resulted in lower uterine weights and, in Kiss1(-/-) mice, lower serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations. Similarly, male Kiss1(-/-) and Gpr54(-/-) mice treated with acyline had smaller testicular sizes and an absence of mature sperm. In addition to examining intact Kiss1(-/-) and Gpr54(-/-) mice, we also assessed the effects of acyline on gonadotrophin concentrations in gonadectomised mice. Gonadectomy resulted in a significant increase in serum FSH concentrations in male Gpr54(-/-) and Kiss1(-/-) mice. Acyline administration to gonadectomised Kiss1(-/-) and Gpr54(-/-) male mice lowered serum FSH and LH concentrations significantly. By contrast to males, gonadectomy did not result in significant gonadotrophin changes in female Kiss1(-/-) and Gpr54(-/-) mice, but acyline administration was followed by a decrease in LH concentrations. These results demonstrate that, although kisspeptin signalling is critical for the high levels of GnRH activity required for normal sexual maturation and

  3. 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 ...

  4. Soluble tumour necrosis factor receptor release after anti-CD3 monoclonal antibody treatment in mice is independent of tumour necrosis factor-alpha release.

    NARCIS (Netherlands)

    Vossen, A.C.T.M.; Tibbe, G.J.M.; Buurman, W.A.; Benner, R.; Savelkoul, H.F.J.

    1996-01-01

    Soluble tumour necrosis factor receptor release after anti-CD3 monoclonal antibody treatment in mice is independent of tumour necrosis factor-alpha release. Vossen AC, Tibbe GJ, Buurman WA, Benner R, Savelkoul HF. Department of Immunology, Erasmus University, Rotterdam, The Netherlands. The

  5. The influence of 17beta-oestradiol on corticotrophin-releasing hormone induced suppression of luteinising hormone pulses and the role of CRH in hypoglycaemic stress-induced suppression of pulsatile LH secretion in the female rat.

    Science.gov (United States)

    Cates, P S; Li, X F; O'Byrne, K T

    2004-06-01

    Corticotrophin-releasing hormone (CRH) released during stress has been implicated in the disruption of the reproductive neuroendocrine axis, and 17beta-oestradiol (E2) has been shown to enhance stress-induced suppression of pulsatile gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) release. The aims of the present study were to examine the role of CRH in hypoglycaemic stress-induced suppression of LH pulses, and to investigate the influence of E2 on the inhibitory effect of CRH on pulsatile LH secretion in the female rat. Suppression of LH pulses by insulin-induced hypoglycaemic (IIH) stress was completely prevented by intracerebroventricular (icv) administration of a CRH antagonist. Central administration of CRH (5 microg) resulted in an interruption of LH pulses in E2 treated animals, but had little or no effect in the absence of this gonadal steroid. These results provide evidence of a pivotal role for CRH in mediating the suppressive effect of IIH stress on pulsatile LH secretion in the female rat, and highlight a sensitising role for E2 in CRH-induced suppression of LH pulses.

  6. 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...

  7. Fibroblast Growth Factor 23 in Postrenal Transplant: An Often Forgotten Hormone.

    Science.gov (United States)

    Amiri, Fateme Shamekhi; Khatami, Mohammad Reza

    2016-12-01

    Fibroblast growth factor 23 is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through fibroblast growth factor receptors and the coreceptor Klotho. In addition to reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, fibroblast growth factor 23 inhibits renal 1α-hydroxylase and stimulates 24-hydroxylase and appears to reduce parathyroid hormone secretion in short-term studies. Fibroblast growth factor 23 synthesis and secretion by osteocytes and osteoblasts are upregulated through 1,25-dihydroxyvitamin D3 and through an increased dietary phosphate intake. Recent studies have indicated that a low-protein diet and calcium deficiency reduce circulating fibroblast growth factor 23 levels, but magnesium deficiency increases fibroblast growth factor levels. Drugs such as phosphate binders, bisphosphonate, and estrogens have various effects on circulating fibroblast growth factor 23 levels. The high cardiovascular disease event rates and mortality associated with elevated levels of this hormone may be due to various effects on the cardiovascular system, including left ventricular hypertrophy, arterial stiffness, vascular calcifications, endothelial dysfunction, and increased levels of inflammatory markers. In addition, elevated levels of this hormone may contribute to mineral bone metabolism disorders and to patient and allograft survival after renal transplant. Here, we discuss the effects of fibroblast growth factor 23 on adverse renal, bone, and cardiovascular outcomes after kidney transplant.

  8. 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.

  9. Supplementation of oligofructose, but not sucralose, decreases high-fat diet induced body weight gain in mice independent of gustducin-mediated gut hormone release.

    Science.gov (United States)

    Steensels, Sandra; Cools, Leen; Avau, Bert; Vancleef, Laurien; Farré, Ricard; Verbeke, Kristin; Depoortere, Inge

    2017-03-01

    Enteroendocrine cells sense nutrients through taste receptors similar to those on the tongue. Sweet and fatty acid taste receptors (FFAR) coupled to the gustatory G-protein, gustducin, on enteroendocrine cells play a role in gut hormone release. We studied if supplementation of artificial (sucralose) or prebiotic (oligofructose; OFS) sweeteners target gustducin-mediated signaling pathways to alter gut hormone release and reduce obesity-associated disorders. Wild-type (WT) and α-gustducin knockout (α-gust -/- ) mice were fed a high-fat diet and gavaged once daily (8 wk) with water or equisweet concentrations of sweeteners. OFS but not sucralose decreased body weight gain (-19 ± 3%, p sucralose, reduced body weight gain and decreased intestinal permeability, but not glucose intolerance. Effects were not mediated by altered gut hormone levels or gustducin-mediated signaling. Artificial sweeteners do not affect gut hormone levels and are metabolically inert in mice on a high-fat diet. In contrast, prebiotic oligosaccharides (OFS) prevent body weight gain but not glucose intolerance. Alterations in sweet and short-chain fatty acid receptors (FFAR) (studied in WT and α-gust -/- mice) that regulate gut hormone levels are not mandatory for the positive effects of OFS. Enhanced uptake of SCFAs may favor interaction with FFAR2/3 on adipose tissue to induce weight loss. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Leptin amplifies the action of thyrotropin-releasing hormone in the solitary nucleus: an in vitro calcium imaging study.

    Science.gov (United States)

    Rogers, Richard C; McDougal, David H; Hermann, Gerlinda E

    2011-04-18

    Leptin exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain-generated thermogenic responses (Hermann et al., 2006). In vivo physiological studies (Rogers et al., 2009) suggested that the thermogenic impact of TRH in the hindbrain is amplified by the action of leptin through a leptin receptor-mediated production of phosphoinositol-trisphosphate [PIP3]. In turn, PIP3 can activate a tyrosine kinase whose target is the Src-SH2 regulatory site on the phospholipase C [PLC] complex. The TRH receptor signals through the PLC complex. Our immunohistochemical studies (Barnes et al., 2010) suggest that this transduction interaction between leptin and TRH occurs within neurons of the solitary nucleus [NST], though this interaction had not been verified. The present in vitro live cell calcium imaging study shows that while medial NST neurons are rarely activated by leptin alone, leptin pre-treatment significantly augments NST neurons' responsiveness to TRH. This leptin-mediated priming of NST neurons was uncoupled by pre-treatment with the phosphoinositide 3-kinase [PI3K] inhibitor [wortmannin], the phospholipase C inhibitor [U73122] and the Src-SH2 antagonist [PP2]. TTX did not eliminate the synergistic response of the agonists, thus the sensitization cannot be attributed to pre-synaptic mechanisms. It seems likely that NST neurons are involved in the leptin-mediated increase in BAT temperature by sensitizing the TRH-PLC-IP3-calcium release mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Interleukin-8 production from human somatotroph adenoma cells is stimulated by interleukin-1β and inhibited by growth hormone releasing hormone and somatostatin

    DEFF Research Database (Denmark)

    Vindeløv, Signe Diness; Hartoft-Nielsen, Marie-Louise; Rasmussen, Åse Krogh

    2011-01-01

    Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin...

  12. A gonadotropin releasing hormone agonist trigger of ovulation with aggressive luteal phase support for patients at risk of ovarian hyperstimulation syndrome undergoing controlled ovarian hyperstimulation.

    Science.gov (United States)

    Liang, I-Ting; Huang, Hong-Yuan; Wu, Hsien-Ming; Wang, Hsin-Shih; Yu, Hsing-Tse; Huang, Shang-Yu; Chang, Chia-Lin; Soong, Yung-Kuei

    2015-10-01

    The aim of this study was to determine the efficacy and safety of luteal phase support using human chorionic gonadotropin (hCG) in cycles that are triggered with a gonadotropin-releasing hormone (GnRH) agonist in a moderate-to-high risk population undergoing a GnRH antagonist protocol. We retrospectively reviewed the charts of patients undergoing an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle with a GnRH antagonist protocol from September 2011 to August 2012. The patients were defined as at high risk for ovarian hyperstimulation syndrome (OHSS) in terms of anti-Müllerian hormone (AMH) and antral follicle counts (AFCs). The patients were divided into two groups depending on whether ovulation was triggered with hCG or a GnRH agonist. Modified luteal support was provided for the cycles triggered by the GnRH agonist via low dose hCG (1500∼5000 IU). For the cycles that were triggered by hCG, urinary hCG (5000 IU) following two doses of recombinant hCG (250 μg) were administered. The primary outcomes of this study were the clinical pregnancy rate and the OHSS rate of the two groups. The secondary outcomes were the number of oocytes retrieved and the number of good quality embryos obtained. The study group and the control group were similar in terms of the primary and secondary outcome measures. Aggressive luteal support with low dose hCG following a GnRH agonist trigger can result in a comparable pregnancy rate to that with the use of a traditional hCG ovulation trigger. However, OHSS can still occur in patients with risk factors. Therefore, other OHSS prevention strategies should be considered. Copyright © 2015. Published by Elsevier B.V.

  13. Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

    Directory of Open Access Journals (Sweden)

    Andreas Bayer

    2017-01-01

    Full Text Available Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs or their clinically related formulations (e.g., Vivostat PRF® came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10 and late (transglutaminase-1 and involucrin differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR- dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.

  14. Factors controlling phosphorus release from sediments in coastal archipelago areas.

    Science.gov (United States)

    Puttonen, Irma; Kohonen, Tuula; Mattila, Johanna

    2016-07-15

    In coastal archipelago areas of the northern Baltic Sea, significantly higher phosphate concentrations (6.0±4.5μmol/l, mean±SD) were measured in water samples close to the sediment surface compared with those from 1m above the seafloor (1.6±2.0μmol/l). The results indicated notable phosphate release from sediments under the bottom water oxygen concentrations of up to 250μmol/l, especially in areas that had experienced recent temporal fluctuation between oxic and hypoxic/anoxic conditions. No single factor alone was found to control the elevated PO4-P concentrations in the near-bottom water. In addition to the oxygen in the water, the contents of potentially mobile phosphorus fractions, grain-size, the organic content at the sediment surface, and the water depth were all important factors controlling the internal loading of phosphorus. The complexity of this process needs to be accounted for in assessments of the internal loading of phosphorus and in potential mitigation plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Factors controlling alkalisalt deposition in recovery boiler- release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P.; Kylloenen, H.; Kurkela, M. [VTT Energy, Espoo (Finland). Process Technology Group

    1996-12-01

    As part of a cooperative effort to develop a model to describe the behaviour of inorganic compounds in kraft recovery boilers, an experimental investigation of the release of sulphur during black liquor pyrolysis has been undertaken. Previous to these studies, the mechanisms of sulphur release and the reasons for the observed effects of process conditions on sulphur release were very poorly understood. On the basis of the experimental results, the main reactions leading to sulphur release have been elucidated with a fair degree of certainty. Logical explanations for the variations of sulphur release with temperature and with liquor solids content have been proposed. The influence of pressure has been investigated in order to gain insights into the effects of mass transfer on the sulphur-release rate. In the near future, the research will be aimed at generating the kinetic data necessary for modelling the release of sulphur in the recovery furnace. (author)

  16. Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors

    NARCIS (Netherlands)

    Usset, J.L.; Raghavan, R.; Tyrer, J.P.; McGuire, V.; Sieh, W.; Webb, P.; Chang-Claude, J.; Rudolph, A.; Anton-Culver, H.; Berchuck, A.; Brinton, L.; Cunningham, J.M.; Defazio, A.; Doherty, J.A.; Edwards, R.P.; Gayther, S.A.; Gentry-Maharaj, A.; Goodman, M.T.; Hogdall, E.; Jensen, A.; Johnatty, S.E.; Kiemeney, L.A.L.M.; Kjaer, S.K.; Larson, M.C.; Lurie, G.; Massuger, L.F.; Menon, U.; Modugno, F.; Moysich, K.B.; Ness, R.B.; Pike, M.C.; Ramus, S.J.; Rossing, M.A.; Rothstein, J.; Song, H.; Thompson, P.J.; Berg, D.J. Van Den; Vierkant, R.A.; Wang-Gohrke, S.; Wentzensen, N.; Whittemore, A.S.; Wilkens, L.R.; Wu, A.H.; Yang, H.; Pearce, C.L.; Schildkraut, J.M.; Pharoah, P.; Goode, E.L.; Fridley, B.L.

    2016-01-01

    BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese

  17. Body image and depression in girls with idiopathic precocious puberty treated with gonadotropin-releasing hormone analogue.

    Science.gov (United States)

    Choi, Min-Seon; Kim, Eun-Young

    2016-09-01

    Precocious puberty (PP) is associated with psychological and behavioral problems. This study aimed to evaluate the perception of body image and depression in girls with PP receiving gonadotropin-releasing hormone (GnRH) analogue therapy. From March to August 2013, 82 girls with PP receiving GnRH analogue therapy were enrolled. Height, weight, body mass index, and stages of pubertal development were assessed. Participants completed a series of questionnaires on their body image perception and pubertal self-assessment. The depression score was calculated using the Korean Kovacs' Children's Depression Inventory. The patients perceived their body to be more obese than the controls did. The mean depression score did not differ between the patients and controls. The mean depression scores according to Tanner stages (1: prepubertal, 2: early pubertal, and 3-5: mid to late pubertal stage) by self-assessment were 5.2±3.6, 6.8±4.9, and 11.4±10.1 (Pbody build and figure (%) and the mean depression scores in patients were: dissatisfied (25.6%, 9.7±7.8) and satisfied (74.4%, 5.5±3.4) (Pbody build and figure were found to significantly affect the depression score(Pbody image and breast development. Such incorrect body image seems to contribute to depression score.

  18. PET Study in a Patient with Spinocerebellar Degeneration before and after Long-Term Administration of Thyrotropin Releasing Hormone

    Directory of Open Access Journals (Sweden)

    H. Tanji

    1996-01-01

    Full Text Available We studied the chronic effect of thyrotropin releasing hormone (TRH in a patient with spinocerebellar degeneration by measuring cerebral metabolic rate for glucose (CMRG1c using 2-[18F]fluoro-2-deoxy-D-glucose (18FDG and positron emission tomography (PET. A 56-year-old female, who had suffered from progressive ataxia for 2 years, was treated by intravenous administration of 2 mg TRH for 3 weeks, and CMRG1c of the brain was measured before and after treatment. CMRG1c was markedly decreased in the cerebellum and there was no significant difference before and after the treatment, i.e. mean CMRG1c values were 4.92 and 4.90 mg/100 g/min, and the ratios of the cerebellum versus the frontal cortex were 0.50 and 0.51, respectively. The degree of disequilibrium of her body examined with stabilography became better by the 19th day and further improved by the 26th day after the start of TRH treatment. Based on the present study we conclude that long-term administration of TRH did not improve CMRG1c in the cerebellum, but evidently improved the sway of gravity center by stabilography. We speculate that the chronic effect of TRH was not necessarily due to an improvement of cerebellar function, because TRH receptors are widely distributed throughout the central nervous system.

  19. Clinical evaluation of thyrotropin-releasing hormone (TRH) test with a sensitive immunoradiometric thyrotropin (TSH) assay kit

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Saeko; Demura, Reiko; Yamanaka, Yukako; Ishiwatari, Naoko; Jibiki, Kazuko; Odagiri, Emi; Demura, Hiroshi

    1987-10-01

    Thyrotropin-releasing hormone (TRH) test was performed using a commercially available immunoradiometric thyrotropin (TSH) assay kit (RIA-gnost hTSH) in patients with endocrine diseases. The basal serum concentration of TSH ranged from 0.2 to 2.9 ..mu..U/ml in healthy subjects. The values for endocrine diseases, except for Graves' disease, were almost within the normal range. A significant increase in TSH values caused by TRH test was observed in females compared with males (4.4 - 24.7 ..mu..U/ml vs 4.1 - 12.3 ..mu..U/ml). In cases of Graves' disease, there was a good correlation between the basal TSH value and the response of TSH to TRH. However, in the other endocrine diseases, including acromegaly, prolactinoma, anorexia nervosa, Cushing syndrome, and hypopituitarism, the response of TSH to TRH did not necessarily correlated with the basal TSH value. TRH test would be of value in elucidating pathophysiologic features, as well as in accurately diagnosing secretion reserve of TSH. (Namekawa, K.).

  20. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH in cystic fibrosis epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nathalie Benz

    Full Text Available Cystic fibrosis (CF, the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(- channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5 directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(- channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R and that GnRH induces an AnxA5 overexpression and an increased Cl(- channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  1. Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY.

    Science.gov (United States)

    Flannery, Brenna M; Clark, Erica S; Pestka, James J

    2012-12-01

    Consumption of deoxynivalenol (DON), a trichothecene mycotoxin known to commonly contaminate grain-based foods, suppresses growth of experimental animals, thus raising concerns over its potential to adversely affect young children. Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown. Here, we tested the hypothesis that DON induces the release of satiety hormones and that this response corresponds to the toxin's anorectic action. Acute ip exposure to DON had no effect on plasma glucagon-like peptide-1, leptin, amylin, pancreatic polypeptide, gastric inhibitory peptide, or ghrelin; however, the toxin was found to robustly elevate peptide YY (PYY) and cholecystokinin (CCK). Specifically, ip exposure to DON at 1 and 5mg/kg bw induced PYY by up to 2.5-fold and CCK by up to 4.1-fold. These responses peaked within 15-120 min and lasted up to 120 min (CCK) and 240 min (PPY), corresponding with depressed rates of food intake. Direct administration of exogenous PYY or CCK similarly caused reduced food intake. Food intake experiments using the NPY2 receptor antagonist BIIE0246 and the CCK1A receptor antagonist devazepide, individually, suggested that PYY mediated DON-induced anorexia but CCK did not. Orolingual exposure to DON induced plasma PYY and CCK elevation and anorexia comparable with that observed for ip exposure. Taken together, these findings suggest that PYY might be one critical mediator of DON-induced anorexia and, ultimately, growth suppression.

  2. Physiology of the gonadotrophin-releasing hormone (GnRH) neurone: studies from embryonic GnRH neurones.

    Science.gov (United States)

    Constantin, S

    2011-06-01

    Gonadotrophin-releasing hormone (GnRH)-secreting neurones are the final output of the central nervous system driving fertility in all mammals. Although it has been known for decades that the efficiency of communication between the hypothalamus and the pituitary depends on the pulsatile profile of GnRH secretion, how GnRH neuronal activity is patterned to generate pulses at the median eminence is unknown. To date, the scattered distribution of the GnRH cell bodies remains the main limitation to assessing the cellular events that could lead to pulsatile GnRH secretion. Taking advantage of the unique developmental feature of GnRH neurones, the nasal explant model allows primary GnRH neurones to be maintained within a micro-network where pulsatile secretion is preserved and where individual cellular activity can be monitored simultaneously across the cell population. This review summarises the data obtained from work using this in vitro model, and brings some insights into GnRH cellular physiology. © 2011 The Author. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  3. Effects of kisspeptin-10 on the electrophysiological manifestation of gonadotropin-releasing hormone pulse generator activity in the female rat.

    Science.gov (United States)

    Kinsey-Jones, James S; Li, Xiao Feng; Luckman, Simon M; O'Byrne, Kevin T

    2008-03-01

    Kisspeptins are extraordinarily potent in stimulating gonadotropic hormone secretion via an action on the hypothalamic GnRH neural system. Because the physiological frequency of the GnRH pulse generator is a critical component of the control system that governs reproductive processes, the aim of this study was to examine the effect of kisspeptin-10 on pulsatile LH secretion and on the electrophysiological manifestation of GnRH pulse generator activity to determine frequency modulatory effects. Adult Sprague Dawley rats were ovariectomized and chronically implanted with electrodes in the arcuate nucleus to record the characteristic increases in hypothalamic multiunit electrical activity volleys coincident with the initiation of each LH pulse measured in peripheral blood and/or indwelling cardiac catheters for the collection of blood samples (25 microl) every 5 min for 6-7 h for the measurement of LH. Intravenous infusion of kisspeptin-10 (7.5, 35, and 100 nmol) induced a dose-dependent increase in LH secretion. The stimulatory effect of kisspeptin-10 (100 nmol) on LH secretion was blocked by the GnRH antagonist cetrorelix, precluding a singular action on gonadotropes. Unexpectedly, however, the marked increase in LH release in response to kisspeptin-10 (100 nmol) administration was not accompanied by any change in multiunit electrical activity volley frequency. It seem unlikely, therefore, that kisspeptin-10 has an appreciable frequency modulatory effect on GnRH pulse generator activity in the female rat.

  4. Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

    Directory of Open Access Journals (Sweden)

    Yssel Mendoza Marí

    2016-01-01

    Full Text Available In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6 proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit’s ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit’s model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

  5. Improvement of chloride transport defect by gonadotropin-releasing hormone (GnRH) in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Benz, Nathalie; Le Hir, Sophie; Norez, Caroline; Kerbiriou, Mathieu; Calvez, Marie-Laure; Becq, Frédéric; Trouvé, Pascal; Férec, Claude

    2014-01-01

    Cystic fibrosis (CF), the most common autosomal recessive disease in Caucasians, is due to mutations in the CFTR gene. F508del, the most frequent mutation in patients, impairs CFTR protein folding and biosynthesis. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) and its traffic to the plasma membrane is altered. Nevertheless, if it reaches the cell surface, it exhibits a Cl(-) channel function despite a short half-life. Pharmacological treatments may target the F508del-CFTR defect directly by binding to the mutant protein or indirectly by altering cellular proteostasis, and promote its plasma membrane targeting and stability. We previously showed that annexine A5 (AnxA5) directly binds to F508del-CFTR and, when overexpressed, promotes its membrane stability, leading to the restoration of some Cl(-) channel function in cells. Because Gonadotropin-Releasing Hormone (GnRH) increases AnxA5 expression in some cells, we tested it in CF cells. We showed that human epithelial cells express GnRH-receptors (GnRH-R) and that GnRH induces an AnxA5 overexpression and an increased Cl(-) channel function in F508del-CFTR cells, due to an increased stability of the protein in the membranes. Beside the numerous physiological implications of the GnRH-R expression in epithelial cells, we propose that a topical use of GnRH is a potential treatment in CF.

  6. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

    Science.gov (United States)

    Bosch, Ernesto; Valencia, Iván; Escudero, Ernesto; Crespo, Juana; Simón, Carlos; Remohí, José; Pellicer, Antonio

    2003-12-01

    To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. Prospective observational study. In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. Cycles were grouped according to serum P level on the day of hCG administration ( or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.

  7. Synthesis and biology of ring-modified l-Histidine containing thyrotropin-releasing hormone (TRH) analogues.

    Science.gov (United States)

    Meena, Chhuttan L; Thakur, Avinash; Nandekar, Prajwal P; Sharma, Shyam S; Sangamwar, Abhay T; Jain, Rahul

    2016-03-23

    Thyrotropin-releasing hormone (TRH) analogues bearing halogen groups (Cl, Br and I) at the C-2 and/or C-5 position, and the alkyl group (CH3, C2H5, C3H7, CH2C6H5) at the N-1 position of the imidazole ring of the central histidine residue were synthesized and evaluated for the receptor binding, calcium mobilization (FLIPR), and IP-1 assay at the HEK mTRHR1 and HEK mTRHR2 expressing cell lines. The most promising analogue 7k showed 925-fold selectivity for HEK mTRH-R2 receptor subtype in the IP-1 assay, 272-fold selectivity for HEK mTRH-R2 receptor subtype in the FLIPR assay, and 21-fold receptor binding specificity at HEK TRH-R2 receptor subtype. The peptide 7k was evaluated in vitro in a brain membrane competitive binding assay, and for stability analysis in the presence of TRH-DE, in vivo. The analogue 7k showed decrease in the sleeping time by more than 76% in a pentobarbital-induced sleeping assay, and showed comparatively less elevation in the TSH level in the blood, in vivo. The computational homology modeling of TRH-R1 and TRH-R2 and docking study with the most potent peptide 7k provide impetus to design CNS specific TRH analogues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Evaluation of the effect of thyrotropin releasing hormone (TRH) on regional cerebral blood flow in spinocerebellar degeneration using 3DSRT.

    Science.gov (United States)

    Kimura, Noriyuki; Kumamoto, Toshihide; Masuda, Teruaki; Nomura, Yuki; Hanaoka, Takuya; Hazama, Yusuke; Okazaki, Toshio; Arakawa, Ryuki

    2009-06-15

    Thyrotropin releasing hormone (TRH) therapy improves cerebellar ataxia in patients with spinocerebellar degeneration (SCD). We investigated the effect of TRH on regional cerebral blood flow (rCBF) using the fully automated region of interest (ROI) technique, 3DSRT. Ten patients with SCD received TRH intravenously (2 mg/day) for 14 days and underwent brain perfusion single photon emission computed tomography before and after therapy. Clinical efficacy was assessed using the International Cooperative Ataxia Rating Scale (ICARS). The rCBF in each ROI was measured using the noninvasive Patlak plot method and calculated using 3DSRT. TRH significantly improved the ICARS scores and increased rCBF in the callosomarginal segment and cerebellum. Cerebellar rCBF increased in 4 of 5 patients with improved ICARS scores and in 3 of 5 patients without improved ICARS scores after TRH therapy. The correlation between the change in cerebellar rCBF and the improved ICARS score, however, was not significant. These findings indicate that TRH therapy may increase cerebellar rCBF in some patients with cerebellar forms of SCD and that 3DSRT may be useful for evaluating the efficacy of TRH for increasing CBF. The beneficial effects of TRH may be due to increased cerebellar rCBF or the increased rCBF may be a secondary effect of TRH therapy.

  9. Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial.

    Science.gov (United States)

    Vercellini, P; Crosignani, P G; Mangioni, C; Imparato, E; Ferrari, A; De Giorgi, O

    1998-11-01

    To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure. A multicentre, prospective, randomised, controlled study. One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks. Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery. Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment. After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P fibroids and uterine volume of 12 to 16 gestational weeks.

  10. Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons

    Directory of Open Access Journals (Sweden)

    Perrine Barraud

    2013-06-01

    Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs. Here, we demonstrate that in homozygous Sox10lacZ/lacZ mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting. Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.

  11. Anti-M?llerian Hormone Is Not Associated with Cardiometabolic Risk Factors in Adolescent Females

    OpenAIRE

    Anderson, E.L.; Fraser, A; McNally, W.; Sattar, N.; Lashen, H.; Fleming, R.; Nelson, S.M.; Lawlor, D.A.

    2013-01-01

    Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.\\ud \\ud Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 ye...

  12. Anti-Mullerian Hormone Is Not Associated with Cardiometabolic Risk Factors in Adolescent Females

    OpenAIRE

    Anderson, E.L.; Fraser, A; McNally, W.; Sattar, N.; Lashen, H.; Fleming, R.; Nelson, S.M.; Lawlor, D.A.

    2013-01-01

    Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is\\ud lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to\\ud assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.\\ud \\ud Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age\\u...

  13. Elevated Plasma Factor IXa Activity in Premenopausal Women on Hormonal Contraception.

    Science.gov (United States)

    Tanratana, Pansakorn; Ellery, Paul; Westmark, Pamela; Mast, Alan E; Sheehan, John P

    2018-01-01

    Combined oral contraceptives induce a reversible hypercoagulable state with an enhanced risk of venous thromboembolism, but the underlying mechanism(s) remain unclear. Subjects on combined oral contraceptives also demonstrate a characteristic resistance to APC (activated protein C) in the thrombin generation assay. Here, we report the potential role of plasma factor IXa (FIXa) as a mechanism for hormone-induced systemic hypercoagulability. A novel assay was used to determine FIXa activity in plasma samples from volunteer blood donors. Plasma from 36 premenopausal females on hormonal contraception and 35 not on hormonal contraception, 35 postmenopausal females, and 10 males were analyzed for FIXa activity, total PS (protein S), total tissue factor pathway inhibitor (TFPI), and TFPI-α antigen. Premenopausal females on hormonal contraception demonstrated significantly increased FIXa activity and decreased TFPI-α compared with the other groups. Remarkably, FIXa values were not normally distributed in the hormonal contraception group, but skewed toward the high end. Plasma FIXa activity inversely correlated with both TFPI-α and total PS antigen. Ex vivo determination of TF-dependent FIX activation in FV-deficient plasma demonstrated that inhibitory anti-TFPI antibodies enhanced FIXa generation by 2- to 3-fold, whereas addition of 75 nmol/L PS reduced FIXa generation by ≈2-fold. Further, increasing FIXa concentration enhanced APC resistance during TF-triggered plasma thrombin generation. Elevation of plasma FIXa activity in association with reductions in TFPI-α and PS is a potential mechanism for systemic hypercoagulability and resistance to APC in premenopausal females on hormonal contraception. © 2017 American Heart Association, Inc.

  14. Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial.

    Science.gov (United States)

    Liu, Jinsheng; Tang, Jiulai

    2017-02-22

    Central precocious puberty (CPP) without organic abnormality is called idiopathic CPP (ICPP). The objective of this trial was to evaluate the effects of pomegranate extract in supplementing gonadotropin-releasing hormone (GnRH) analog therapy on ICPP-affected girls in the Chinese population. 286 girls, diagnosed with ICPP were initially enrolled into this trial, and among them 225 eligible patients were randomized to receive a combinational GnRH analog treatment supplemented with either a placebo or pomegranate extract on a daily basis for a period of 3 months. Their demographics, secondary sexual characteristics and hormone profiles were analyzed at baseline and end of trial. After 3 months of treatment, demographic profiles including bone age, growth velocity and height standard deviation score for bone age, and secondary sexual characteristics including uterus and ovary volume, as well as serum hormone profiles including estradiol, peak luteinizing hormone and insulin-like growth factor 1 were all significantly improved in girls receiving a combinational treatment of both GnRH analog and pomegranate extract. Daily consumption of pomegranate extract was able to supplement and improve the treatment outcomes of the GnRH analog therapy for ICPP in Chinese girls.

  15. Prenatal development of gonadotropin-releasing hormone receptors in the rat anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Jennes, L. (Wright State Univ. School of Medicine, Dayton, OH (USA))

    1990-02-01

    The development of pituitary GnRH receptors was studied in the rat with in vitro and in vivo autoradiography. GnRH receptors were first seen in pituitary primordia of 13-day-old fetuses. The binding was specific and saturable and was abolished in the presence of 10 microM synthetic GnRH. To examine whether GnRH was available to the fetus, amnionic fluid was collected on days E 12-18. RIA analyses showed that GnRH levels in the amnionic fluid were low on days 12 and 13 (0-20 pM/ml) and rose to 225 pM/ml on day E 16 before they declined to 110 pM/ml on fetal day E 18. The highest levels of GnRH in the amnionic fluid on day E 16 coincided with the first appearance of immunoreactive LH cells, as determined by immunohistochemistry. Intravenous injection of 500 microliters amnionic fluid into pentobarbital-anesthetized adult rats caused a transient 40-60% increase in circulating serum LH in the recipient animal. To show that GnRH from the amnionic fluid has access to the developing pituitary, the 125I-labeled GnRH agonist Buserelin was injected into the amnionic fluid of 13-, 14-, and 15-day-old fetuses in the presence or absence of 10 microM unlabeled GnRH. Autoradiographic analysis of the fetal tissue indicated that the labeled GnRH agonist bound to specific receptors in the primordial pituitaries. The results suggest that the pituitary gonadotropes are differentiated before day E 13 because the expression of GnRH receptors is already an indication of cell determination. Since GnRH is present in the amnionic fluid in a biologically active form and can reach the fetal pituitary, it is concluded that GnRH may be an important factor determining the onset LH synthesis, but not the differentiation, of primordial pituitary cells.

  16. Synergistic effect of cortisol and thyrotrophin releasing hormone on lung maturation in the fetal sheep entails connective tissue maturation.

    Science.gov (United States)

    Campos, G A; Guerra, F A; Brümmer, E; Muñoz, M L; Vega, I A

    1992-01-01

    Pressure-volume relationships and collagen and elastin contents were measured in the lungs of fetal sheep infused either with saline (n = 4), thyrotrophin-releasing hormone (TRH; n = 6), cortisol (n = 9) or TRH plus cortisol (n = 10) at 128 days of gestation (term = 149 days) for 7 days. Lung distensibility (V40 = 1.8 +/- 0.1 ml/g wet wt; mean +/- SD) and stability (V5 = 0.6 +/- 0.1) increased along with collagen (C) (10.1 +/- 2.7 micrograms/mg) and elastin (E) contents (128 +/- 35 ng/mg) in the animals infused with TRH plus cortisol and were significantly higher (p < 0.05) than those observed in TRH (V40 0.62 +/- 0.07; V5 0.32 +/- 0.04; C 3.53 +/- 1.3; E 38.2 +/- 8.3), cortisol (V4 0.66 +/- 0.6; V5 0.27 +/- 0.03; C 4.27 +/- 0.8; E 41.02 +/- 12.7) or saline infused fetuses (V40 0.40 +/- 0.1; V5 0.20 +/- 0.06; C 3.28 +/- 0.9; E 31.5 +/- 9.2). Plasma concentrations of prolactin (PRL), triiodothyronine (T3) and cortisol (F) were also higher in the group of fetuses infused with both hormones in comparison with the other groups. In fetuses treated with TRH plus cortisol, PRL (32 +/- 8.3 ng/ml) and T3 (308.3 +/- 36 micrograms/dl) were significantly higher than in those infused with cortisol alone (PRL 3.7 +/- 2.3; T3 128 +/- 30) or with saline (PRL 4.2 +/- 1.6; T3 < 5 micrograms/dl). In the group treated with TRH alone, PRL also increased significantly (37 +/- 6.4), but T3 increased only slightly (18 +/- 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effects of active and passive gonadotrophin-releasing hormone immunization on recognition and establishment of pregnancy in pigs.

    Science.gov (United States)

    Tast, A; Love, R J; Clarke, I J; Evans, G

    2000-01-01

    This study investigated the effects of a reduction in gonadotrophins, by means of differently timed active and passive gonadotrophin-releasing hormone (GnRH) immunization at various stages, on the maintenance of early pregnancy in pigs. In the first experiment crossbred sows (n = 11) were immunized against GnRH using a commercial vaccine on the day of farrowing, mated at the first oestrus, and a booster immunization was administered 10 days (n = 7) or 20 days (n = 4) after mating. Plasma samples were collected every second day and assayed for GnRH antibodies and progesterone. Pregnancy testing was carried out by real time ultrasound. None of the sows receiving the booster immunization 10 days after mating were pregnant on Day 18 after mating. All sows receiving the booster on Day 20 after mating aborted, with a mean vaccination-to-abortion interval of 10.0 +/- 1.5 days. In the second experiment, crossbred gilts (n = 6) were passively immunized by infusing (i.v.) GnRH immune pig serum on Day 12 after mating. Luteinizing hormone profiles were determined on the day before immunization and one day afterwards. Daily plasma samples were assayed for GnRH antibodies and progesterone. None of the gilts were pregnant 18 days after mating, compared with 5 of 6 non-immunized controls. Booster immunization 10 days after mating resulted in failure of embryonic development and establishment of pregnancy before the corpora lutea (CL) regressed, according to progesterone profiles, whereas immunization 20 days after mating resulted in regression of CL followed by abortion. Passive immunization 12 days after mating had a similar effect to the active immunization 10 days after mating. These results demonstrate two different outcomes of active GnRH immunization depending on the timing of immunization, and indicate that loss of pregnancy between Days 12 and 18 may occur due a reduction in progesterone rather than complete failure of the CL, as occurs at later stages. The findings may

  18. Has active immunization against gonadotrophin-releasing hormone any effect on testis innervation in the pig? An immunohistochemical study.

    Science.gov (United States)

    Sienkiewicz, W; Molenaar, G J; Kaleczyc, J; Falkowski, J; Lakomy, M

    2000-08-01

    The innervation of porcine testes was studied in intact animals and in boars undergoing active immunization against gonadotrophin-releasing hormone (GnRH) by means of immunohistochemistry using antibodies to tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), vasoactive intestinal polypolypeptide (VIP), neuropeptide Y (NPY), synaptosome-associated protein of 25 kDa (SNAP-25) and protein gene product 9.5 (PGP 9.5). Moreover, the distribution of luteinizing hormone (LH) receptors in clusters of Leydig cells was also investigated. To identify these cells easily, either the NADPH-diaphorase histochemical technique or the Mayer counter-staining procedure was applied. Differences in the distribution pattern and relative density of particular subsets of intratesticular nerve fibres were observed in immunized boars as compared to those found in the intact animals. In the testes of non-treated animals, only single TH-immunoreactive (TH-IR) nerve fibres were observed. However, many D beta H-IR nerve terminals surrounded blood vessels in the tunica albuginea and parenchyma. Very scarce VIP-IR nerves occurred only in the tunica albuginea, mainly in close vicinity to blood vessels. Immunoreactivity to NPY occurred in single nerve fibres. Immunoreactivity to SNAP-25 and PGP 9.5 was found in single nerve fibres distributed mainly in the tunica albuginea. The interstitial cells were heavily stained for LH-receptors and NADPH-diaphorase. In the testes of immunized animals, only single TH-IR nerve fibres, scattered mainly in the tunica albuginea, were observed. Some TH-IR nerve terminals were also encountered in the parenchyma of the organ, where they were always associated with blood vessels. D beta H-IR nerve fibres formed a dense network distributed throughout the testis in association with the capsule, vasculature and interstitium. Some fibres were observed to run between seminiferous tubules. VIP-IR nerve fibres were located in the neighbourhood of blood vessels in

  19. Interactions of familial and hormonal risk factors for large bowel cancer in women.

    Science.gov (United States)

    Newcomb, P A; Taylor, J O; Trentham-Dietz, A

    1999-08-01

    Family history of colorectal cancer has been consistently associated with an increased personal risk of this disease. Since evidence suggests that hormones are related to colon cancer risk in women, the effect of family history on large bowel incidence may be modified according to endogenous and exogenous hormone levels. We analysed data from a population-based case-control study of female colorectal cancer to evaluate family history and cancer risk. Cases (n = 702) were female residents of Wisconsin with a new diagnosis of colorectal cancer, identified through a statewide tumour registry. Controls (n = 2274) were randomly selected from lists of licensed drivers and from rosters of Medicare beneficiaries. All relative risks (RR) were adjusted for age, body mass index, smoking and alcohol history, education, and use of hormone replacement therapy. Compared with women who reported no history of cancer in a first degree relative, women with a family history had an RR of 2.07 (95% confidence interval [CI]: 1.60-2.68). Regardless of which parent was affected, risks were increased about twofold, while sibling history was associated with about a 50% increase in risk. Risk was greater if more than one family member was affected (RR 3.65, 95% CI: 1.81-7.37). The association between family history and risk was stronger for colon cancer than for rectal cancer. There were no indications that exogenous hormonal factors, notably hormone replacement use, modified these risks. There was a suggestion that high parity attenuated the risks associated with family history (P = 0.07). These results confirm that family history of colorectal cancer is associated with a doubling of risk for large bowel cancer in women; some histories were associated with greater risk. This relation was not substantially different among subgroups of women with varying exogenous and endogenous hormone exposures.

  20. Macrophage migration inhibitory factor (MIF) and thyroid hormone alterations in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

    Science.gov (United States)

    Wendt, Mårten; Börjesson, Ola; Avik, Aune; Bratt, Johan; Anderstam, Björn; Qureshi, Abdul R; Miller, Edmund J; Gunnarsson, Iva; Bruchfeld, Annette

    2013-05-20

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine known to be released from lymphocytes, macrophages and endothelial cells and also in animal models shown to be inducible with glucocorticoids (GC). In contrast, thyroxine seems to antagonize MIF activity. To investigate whether MIF is increased in active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and possible correlations with GC dosing and thyroid hormone levels, 27 consecutive patients with active AAV were studied and followed prospectively. Disease activity was assessed using Birmingham Vasculitis Activity Score 2003 (BVAS) at baseline and at follow-up at 3 and 6 months, along with MIF, thyroid hormones free triiodothyronine (fT3) and free thyroxine (fT4), C-reactive protein (CRP) and creatinine. MIF was elevated significantly at baseline compared with follow-up at 3 and 6 months (8,618 pg/mL versus 5,696 and 6,212 respectively; P < 0.002) but did not correlate to CRP, GC dose, creatinine or organ involvement. fT3 was depressed significantly at baseline compared with follow-up (1.99 pg/mL versus 2.31 and 2.67 respectively; P = 0.01) and correlated inversely to the BVAS score at baseline. We found a significant correlation between the MIF/fT4 ratio at baseline versus MIF/fT4 ratio at 6 months (ρ = 0.52, P < 0.005) and a trend between the baseline MIF/fT3 ratio versus MIF/fT3 ratio at 6 months (ρ = 0.39, P = 0.05). These results suggest a possible role for MIF and thyroid status in AAV. Further studies could reveal whether the association between AAV and thyroid hormone levels in the context of elevated MIF may present a link as well as a target of treatment.

  1. Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors

    OpenAIRE

    Eraslan, Evren; Akyazi, Ibrahim; Erg?l-Ekiz, Elif; Matur, Erdal

    2015-01-01

    Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chro...

  2. Dissociable Role of Corticotropin Releasing Hormone Receptor Subtype 1 on Dopaminergic and D1 Dopaminoceptive Neurons in Cocaine Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Rick E. Bernardi

    2017-11-01

    Full Text Available The ability of many drugs of abuse, including cocaine, to mediate reinforcement and drug-seeking behaviors is in part mediated by the corticotropin-releasing hormone (CRH system, in which CRH exerts its effects partly via the CRH receptor subtype 1 (CRHR1 in extra-hypothalamic areas. In fact, CRHR1 expressed in regions of the mesolimbic dopamine (DA system have been demonstrated to modify cocaine-induced DA release and alter cocaine-mediated behaviors. Here we examined the role of neuronal selectivity of CRHR1 within the mesolimbic system on cocaine-induced behaviors. First we used a transgenic mouse line expressing GFP under the control of the Crhr1 promoter for double fluorescence immunohistochemistry to demonstrate the cellular location of CRHR1 in both dopaminergic and D1 dopaminoceptive neurons. We then studied cocaine sensitization, self-administration, and reinstatement in inducible CRHR1 knockouts using the CreERT2/loxP in either dopamine transporter (DAT-containing neurons (DAT-Crhr1 or dopamine receptor 1 (D1-containing neurons (D1-Crhr1. For sensitization testing, mice received five daily injections of cocaine (15 mg/kg IP. For self-administration, mice received eight daily 2 h cocaine (0.5 mg/kg per infusion self-administration sessions followed by extinction and reinstatement testing. There were no differences in the acute or sensitized locomotor response to cocaine in DAT-Crhr1 or D1-Crhr1 mice and their respective controls. Furthermore, both DAT-Crhr1 and D1-Crhr1 mice reliably self-administered cocaine at the level of controls. However, DAT-Crhr1 mice demonstrated a significant increase in cue-induced reinstatement relative to controls, whereas D1-Crhr1 mice demonstrated a significant decrease in cue-induced reinstatement relative to controls. These data demonstrate the involvement of CRHR1 in cue-induced reinstatement following cocaine self-administration, and implicate a bi-directional role of CRHR1 for cocaine craving.

  3. Dissociable Role of Corticotropin Releasing Hormone Receptor Subtype 1 on Dopaminergic and D1 Dopaminoceptive Neurons in Cocaine Seeking Behavior.

    Science.gov (United States)

    Bernardi, Rick E; Broccoli, Laura; Hirth, Natalie; Justice, Nicholas J; Deussing, Jan M; Hansson, Anita C; Spanagel, Rainer

    2017-01-01

    The ability of many drugs of abuse, including cocaine, to mediate reinforcement and drug-seeking behaviors is in part mediated by the corticotropin-releasing hormone (CRH) system, in which CRH exerts its effects partly via the CRH receptor subtype 1 (CRHR1) in extra-hypothalamic areas. In fact, CRHR1 expressed in regions of the mesolimbic dopamine (DA) system have been demonstrated to modify cocaine-induced DA release and alter cocaine-mediated behaviors. Here we examined the role of neuronal selectivity of CRHR1 within the mesolimbic system on cocaine-induced behaviors. First we used a transgenic mouse line expressing GFP under the control of the Crhr1 promoter for double fluorescence immunohistochemistry to demonstrate the cellular location of CRHR1 in both dopaminergic and D1 dopaminoceptive neurons. We then studied cocaine sensitization, self-administration, and reinstatement in inducible CRHR1 knockouts using the CreERT2/loxP in either dopamine transporter (DAT)-containing neurons (DAT-Crhr1) or dopamine receptor 1 (D1)-containing neurons (D1-Crhr1). For sensitization testing, mice received five daily injections of cocaine (15 mg/kg IP). For self-administration, mice received eight daily 2 h cocaine (0.5 mg/kg per infusion) self-administration sessions followed by extinction and reinstatement testing. There were no differences in the acute or sensitized locomotor response to cocaine in DAT-Crhr1 or D1-Crhr1 mice and their respective controls. Furthermore, both DAT-Crhr1 and D1-Crhr1 mice reliably self-administered cocaine at the level of controls. However, DAT-Crhr1 mice demonstrated a significant increase in cue-induced reinstatement relative to controls, whereas D1-Crhr1 mice demonstrated a significant decrease in cue-induced reinstatement relative to controls. These data demonstrate the involvement of CRHR1 in cue-induced reinstatement following cocaine self-administration, and implicate a bi-directional role of CRHR1 for cocaine craving.

  4. Body image and depression in girls with idiopathic precocious puberty treated with gonadotropin-releasing hormone analogue

    Directory of Open Access Journals (Sweden)

    Min-Seon Choi

    2016-09-01

    Full Text Available PurposePrecocious puberty (PP is associated with psychological and behavioral problems. This study aimed to evaluate the perception of body image and depression in girls with PP receiving gonadotropin-releasing hormone (GnRH analogue therapy.MethodsFrom March to August 2013, 82 girls with PP receiving GnRH analogue therapy were enrolled. Height, weight, body mass index, and stages of pubertal development were assessed. Participants completed a series of questionnaires on their body image perception and pubertal self-assessment. The depression score was calculated using the Korean Kovacs' Children's Depression Inventory.ResultsThe patients perceived their body to be more obese than the controls did. The mean depression score did not differ between the patients and controls. The mean depression scores according to Tanner stages (1: prepubertal, 2: early pubertal, and 3–5: mid to late pubertal stage by self-assessment were 5.2±3.6, 6.8±4.9, and 11.4±10.1 (P<0.05, respectively. The perception of overall body build and figure (% and the mean depression scores in patients were: dissatisfied (25.6%, 9.7±7.8 and satisfied (74.4%, 5.5±3.4 (P<0.05. In multiple linear regression analysis, self-T3 (Tanner stage 3–5 by self-awareness and dissatisfaction about overall body build and figure were found to significantly affect the depression score(P<0.05.ConclusionThe perception of pubertal status and satisfaction about height or weight are unrelated to objective physical findings. Patients with PP are prone to distorted perception about their body image and breast development. Such incorrect body image seems to contribute to depression score.

  5. Bmal1 knockdown suppresses wake and increases immobility without altering orexin A, corticotrophin-releasing hormone, or glutamate decarboxylase.

    Science.gov (United States)

    Akladious, Afaf; Azzam, Sausan; Hu, Yufen; Feng, Pingfu

    2018-02-14

    To determine the effect of Bmal1 knockdown (KD) on sleep, activity, immobility, hypothalamic levels of orexin, corticotrophin-releasing hormone (CRH), and GABAergic glutamate decarboxylase (GAD). We used Bmal1 siRNA, or control siRNA intracerebroventricular (ICV) injection to knock down Bmal1 in C57BL/6 mice. Sleep polysomnography, wheel-running activity, and tail suspension test were performed. Polysomnographic (PSG) recordings in both groups were preceded by ICV injection made during both the light phase and the dark phase. We also measured brain orexin A and CRH using an ELISA and measured GAD using immunoblotting. Compared with control group, Bmal1 KD group had reduced wheel activity and increased immobility. Compared with control, the Bmal1 KD group had reduced wheel activity and increased immobility. During the first 24 hours after treatment, we observed that control siRNA induced a much greater increase in sleep during the dark phase, which was associated with lower orexin levels. However, beginning 24 hours after treatment, we observed an increase in sleep and a decrease in time spent awake during the dark phase in the Bmal1 KD group. These changes were not associated with changes in brain levels of orexin A, CRH, or GAD. Bmal1 KD led to reduced activity, increased immobility, and dramatic reduction in time spent awake as well as an increase in sleep during the dark phase. Early after injection, there was a slight change in sleep but brain levels of orexin, CRH, and GAD remain unchanged. Control siRNA also affected sleep associated with changes in orexin levels. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  6. The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane.

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    Michelle Re

    Full Text Available The mammalian type I gonadotropin releasing hormone receptor (GnRH-R is a structurally unique G protein-coupled receptor (GPCR that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME. Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor.

  7. The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study.

    Science.gov (United States)

    Kwako, Laura E; Spagnolo, Primavera A; Schwandt, Melanie L; Thorsell, Annika; George, David T; Momenan, Reza; Rio, Daniel E; Huestis, Marilyn; Anizan, Sebastien; Concheiro, Marta; Sinha, Rajita; Heilig, Markus

    2015-03-13

    Extensive preclinical data implicate corticotropin-releasing hormone (CRH), acting through its CRH1 receptor, in stress- and dependence-induced alcohol seeking. We evaluated pexacerfont, an orally available, brain penetrant CRH1 antagonist for its ability to suppress stress-induced alcohol craving and brain responses in treatment seeking alcohol-dependent patients in early abstinence. Fifty-four anxious alcohol-dependent participants were admitted to an inpatient unit at the NIH Clinical Center, completed withdrawal treatment, and were enrolled in a double-blind, randomized, placebo-controlled study with pexacerfont (300 mg/day for 7 days, followed by 100 mg/day for 23 days). After reaching steady state, participants were assessed for alcohol craving in response to stressful or alcohol-related cues, neuroendocrine responses to these stimuli, and functional magnetic resonance imaging (fMRI) responses to alcohol-related stimuli or stimuli with positive or negative emotional valence. A separate group of 10 patients received open-label pexacerfont following the same dosing regimen and had cerebrospinal fluid sampled to estimate central nervous system exposure. Pexacerfont treatment had no effect on alcohol craving, emotional responses, or anxiety. There was no effect of pexacerfont on neural responses to alcohol-related or affective stimuli. These results were obtained despite drug levels in cerebrospinal fluid (CSF) that predict close to 90% central CRH1 receptor occupancy. CRH1 antagonists have been grouped based on their receptor dissociation kinetics, with pexacerfont falling in a category characterized by fast dissociation. Our results may indicate that antagonists with slow offset are required for therapeutic efficacy. Alternatively, the extensive preclinical data on CRH1 antagonism as a mechanism to suppress alcohol seeking may not translate to humans.

  8. Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.

    Science.gov (United States)

    Purba, J S; Raadsheer, F C; Hofman, M A; Ravid, R; Polman, C H; Kamphorst, W; Swaab, D F

    1995-07-01

    Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous recovery from EAE. The HPA axis activity is regulated by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are localized in the paraventricular nucleus (PVN) of the hypothalamus. We determined the number of immunocytochemically identified CRH-immunoreactive (CRH-IR) and AVP-immunoreactive (AVP-IR) neurons in the PVN of the human hypothalamus of 8 MS patients, aged 34-63 years, and 8 age-matched control subjects without any primary neurological or psychiatric disorders, aged 30-59 years. In addition, the number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since these neurons innervate brain stem nuclei and might thus be related to autonomic disturbances in MS. In MS the staining intensity for AVP was clearly lower and for OXT slightly lower. For CRH, the staining intensity was similar in both groups, and, moreover, in MS patients the number of CRH-IR cells in the PVN was found to be about 2.4 times higher than that in the control group. The number of OXT-IR or AVP-IR cells in the PVN of MS patients was not significantly different from that of the control group. Our results point to an activation of the neuroendocrine HPA axis which may be compatible with the idea that the HPA axis is involved in recovery from MS.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome.

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    Ayaka Sasaki

    Full Text Available Irritable bowel syndrome (IBS is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropin-releasing hormone (CRH. Although some candidate genes have been identified in stress-related disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs in CRH-related genes influence the features of IBS.In total, 253 individuals (123 men and 130 women participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258 and CRH-binding protein (CRH-BP (rs10474485 were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale.Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers.These results suggest that the CRH and CRH-BP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.

  10. Humoral immune responses against gonadotropin releasing hormone elicited by immunization with phage-peptide constructs obtained via phage display.

    Science.gov (United States)

    Samoylov, Alexandre; Cochran, Anna; Schemera, Bettina; Kutzler, Michelle; Donovan, Caitlin; Petrenko, Valery; Bartol, Frank; Samoylova, Tatiana

    2015-12-20

    Phage display is based on genetic engineering of phage coat proteins resulting in fusion peptides displayed on the surface of phage particles. The technology is widely used for generation of phages with novel characteristics for numerous applications in biomedicine and far beyond. The focus of this study was on development of phage-peptide constructs that stimulate production of antibodies against gonadotropin releasing hormone (GnRH). Phage-peptide constructs that elicit production of neutralizing GnRH antibodies can be used for anti-fertility and anti-cancer applications. Phage-GnRH constructs were generated via selection from a phage display library using several types of GnRH antibodies as selection targets. Such phage constructs were characterized for sequence similarities to GnRH peptide and frequency of their occurrence in the selection rounds. Five of the constructs with suitable characteristics were tested in mice as a single dose 5×10(11) virions (vir) vaccine and were found to be able to stimulate production of GnRH-specific antibodies, but not to suppress testosterone (indirect indicator of GnRH antibody neutralizing properties). Next, one of the constructs was tested at a higher dose of 2×10(12) vir per mouse in combination with a poly(lactide-co-glycolide) (PLGA)-based adjuvant. This resulted in multifold increase in GnRH antibody production and significant reduction of serum testosterone, indicating that antibodies produced in response to the phage-GnRH immunization possess neutralizing properties. To achieve optimal immune responses for desired applications, phage-GnRH constructs can be modified with respect to flanking sequences of GnRH-like peptides displayed on phage. Anticipated therapeutic effects also might be attained using optimized phage doses, a combination of several constructs in a single treatment, or application of adjuvants and advanced phage delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Brain morphology and immunohistochemical localization of the gonadotropin-releasing hormone in the bluefin tuna, Thunnus thynnus

    Directory of Open Access Journals (Sweden)

    G Palmieri

    2009-08-01

    Full Text Available The present study was focused on the morphology of the diencephalic nuclei (likely involved in reproductive functions as well as on the distribution of GnRH (gonadotropin-releasing hormone in the rhinencephalon, telencephalon and the diencephalon of the brain of bluefin tuna (Thunnus thynnus by means of immunohistochemistry. Bluefin tuna has an encephalization quotient (QE similar to that of other large pelagic fish. Its brain exhibits well-developed optic tecta and corpus cerebelli. The diencephalic neuron cell bodies involved in reproductive functions are grouped in two main nuclei: the nucleus preopticus-periventricularis and the nucleus lateralis tuberis. The nucleus preopticus-periventricularis consists of the nucleus periventricularis and the nucleus preopticus consisting of a few sparse multipolar neurons in the rostral part and numerous cells closely packed and arranged in several layers in its aboral part. The nucleus lateralis tuberis is located in the ventral-lateral area of the diencephalon and is made up of a number of large multipolar neurones. Four different polyclonal primary antibodies against salmon (sGnRH, chicken (cGnRH-II (cGnRH-II 675, cGnRH-II 6 and sea bream (sbGnRH were employed in the immunohistochemical experiments. No immunoreactive structures were found with anti sbGnRH serum. sGnRH and cGnRH-II antisera revealed immunoreactivity in the perikarya of the olfactory bulbs, preopticus-periventricular nucleus, oculomotor nucleus and midbrain tegmentum. The nucleus lateralis tuberis showed immunostaining only with anti-sGnRH serum. Nerve fibres immunoreactive to cGnRH and sGnRH sera were found in the olfactory bulbs, olfactory nerve and neurohypophysis. The significance of the distribution of the GnRHimmunoreactive neuronal structures is discussed.

  12. Distribution of hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons in the hypothalamic paraventricular nucleus of the mouse.

    Science.gov (United States)

    Kádár, Andrea; Sánchez, Edith; Wittmann, Gábor; Singru, Praful S; Füzesi, Tamás; Marsili, Alessandro; Larsen, P Reed; Liposits, Zsolt; Lechan, Ronald M; Fekete, Csaba

    2010-10-01

    Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central regulators of the hypothalamic-pituitary-thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non-hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double- and triple-labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitoneally with the retrograde tracer Fluoro-Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid-level of the PVN, primarily in the compact part. In this part of the PVN, TRH neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co-localization of TRH and cocaine- and amphetamine-regulated transcript (CART) were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid-level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid-level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats.

  13. Association of corticotropin releasing hormone receptor 2 (CRHR2) genetic variants with acute bronchodilator response in asthma

    Science.gov (United States)

    Poon, Audrey H.; Tantisira, Kelan G.; Litonjua, Augusto A.; Lazarus, Ross; Xu, Jingsong; Lasky-Su, Jessica; Lima, John J.; Irvin, Charles G.; Hanrahan, John P.; Lange, Christoph; Weiss, Scott T.

    2011-01-01

    Objective Corticotropin - releasing hormone receptor 2 (CRHR2) participates in smooth muscle relaxation response and may influence acute airway bronchodilator response to short – acting β2 agonist treatment of asthma. We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in asthma. Methods We investigated 28 single nucleotide polymorphisms in CRHR2 for associations with acute bronchodilator response to albuterol in 607 Caucasian asthmatic subjects recruited as part of the Childhood Asthma Management Program (CAMP). Replication was conducted in two Caucasian adult asthma cohorts – a cohort of 427 subjects enrolled in a completed clinical trial conducted by Sepracor Inc. (MA, USA) and a cohort of 152 subjects enrolled in the Clinical Trial of Low-Dose Theopylline and Montelukast (LODO) conducted by the American Lung Association Asthma Clinical Research Centers. Results Five variants were significantly associated with acute bronchodilator response in at least one cohort (p-value ≤ 0.05). Variant rs7793837 was associated in CAMP and LODO (p-value = 0.05 and 0.03, respectively) and haplotype blocks residing at the 5’ end of CRHR2 were associated with response in all three cohorts. Conclusion We report for the first time, at the gene level, replicated associations between CRHR2 and acute bronchodilator response. While no single variant was significantly associated in all three cohorts, the findings that variants at the 5’ end of CRHR2 are associated in each of three cohorts strongly suggest that the causative variants reside in this region and its genetic effect, although present, is likely to be weak. PMID:18408560

  14. Peri-pubertal gonadotropin-releasing hormone analog treatment affects hippocampus gene expression without changing spatial orientation in young sheep.

    Science.gov (United States)

    Nuruddin, Syed; Wojniusz, Slawomir; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P; Robinson, Jane E; Solbakk, Anne-Kristin; Amiry-Moghaddam, Mahmood; Haraldsen, Ira Ronit Hebold

    2013-04-01

    Normal brain maturation is the result of molecular changes that can be modulated by endocrine variables associated with brain plasticity and results in sex- and age specific changes in cognitive performance. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control. In this study we explore effects of this treatment regime on hippocampal gene expression and spatial orientation. The study was conducted with 30 same-sex twin lambs, half of which were treated with the GnRH analog (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. Animals were tested in their spatial orientation ability at 48 weeks of age. Quantitative real time PCR analysis was conducted to examine effects of treatment on the expression of genes associated with synaptic plasticity and endocrine signaling. GnRHa treatment was associated with significant sex- and hemisphere specific changes in mRNA expression for some of the genes studied. The treatment had no significant effect on spatial orientation. However, there was a tendency that females performed better than males in spatial orientation. Our results indicate that GnRH directly and/or indirectly, is involved in the regulation of sex- and side-specific expression patterns of genes. Hence, these results should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers:

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Rookus, Matti; Andrieu, Nadine

    2009-01-01

    BACKGROUND: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated...... in a small number of studies. METHODS: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox...... proportional hazards framework. RESULTS: There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had...

  16. Relative effectiveness of carp pituitary extract, luteinizing hormone releasing hormone analog LHRHa injections and LHRHa implants for producing hybrid catfish fry

    Science.gov (United States)

    Adoption of the hybrid catfish (channel catfish, Ictalruus punctatus, female x blue catfish, I. furcatus, male) is increasing in the catfish industry. The most effective way to produce fry is hormone induced spawning of females coupled with hand stripping and in vitro fertilization. The success of...

  17. Internal jugular vein: Peripheral vein adrenocorticotropic hormone ratio in patients with adrenocorticotropic hormone-dependent Cushing′s syndrome: Ratio calculated from one adrenocorticotropic hormone sample each from right and left internal jugular vein during corticotrophin releasing hormone stimulation test

    Directory of Open Access Journals (Sweden)

    Sachin Chittawar

    2013-01-01

    Full Text Available Background: Demonstration of central: Peripheral adrenocorticotropic hormone (ACTH gradient is important for diagnosis of Cushing′s disease. Aim: The aim was to assess the utility of internal jugular vein (IJV: Peripheral vein ACTH ratio for diagnosis of Cushing′s disease. Materials and Methods: Patients with ACTH-dependent Cushing′s syndrome (CS patients were the subjects for this study. One blood sample each was collected from right and left IJV following intravenous hCRH at 3 and 5 min, respectively. A simultaneous peripheral vein sample was also collected with each IJV sample for calculation of IJV: Peripheral vein ACTH ratio. IJV sample collection was done under ultrasound guidance. ACTH was assayed using electrochemiluminescence immunoassay (ECLIA. Results: Thirty-two patients participated in this study. The IJV: Peripheral vein ACTH ratio ranged from 1.07 to 6.99 ( n = 32. It was more than 1.6 in 23 patients. Cushing′s disease could be confirmed in 20 of the 23 cases with IJV: Peripheral vein ratio more than 1.6. Four patients with Cushing′s disease and 2 patients with ectopic ACTH syndrome had IJV: Peripheral vein ACTH ratio less than 1.6. Six cases with unknown ACTH source were excluded for calculation of sensitivity and specificity of the test. Conclusion: IJV: Peripheral vein ACTH ratio calculated from a single sample from each IJV obtained after hCRH had 83% sensitivity and 100% specificity for diagnosis of CD.

  18. Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE.

    Science.gov (United States)

    Brod, Staley A; Bauer, Victoria

    2013-01-01

    Ingested immunoactive proteins type I IFN, SIRS peptide 1-21, α-MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T(reg) cell frequencies. We examined whether another protein, thyrotropin releasing factor (TRH), would have similar anti-inflammatory effects in EAE after oral administration. B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TRH during ongoing disease. Splenocytes from mock fed or TRH fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Ingested (oral) TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TRH fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF-α cytokines in both the spleen and the CNS. In recipients of donor cells from TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in T(reg) cell frequencies in actively fed or recipients of TRH fed donor cells. Ingested (orally administered) TRH can inhibit clinical disease, inhibit CNS inflammation by decreasing Th1-like, Th17 and TNF-α cytokines and increasing Th2-like cytokines (IL-13) in the CNS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Use and Effectiveness of Gonadotropin-Releasing Hormone Agonists for Prophylactic Menstrual Suppression in Postmenarchal Women Who Undergo Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Poorvu, Philip D; Barton, Sara E; Duncan, Christine N; London, Wendy B; Laufer, Marc R; Lehmann, Leslie E; Marcus, Karen J

    2016-06-01

    To describe the rates of use and effectiveness of gonadotropin-releasing hormone (GnRH) agonists and other forms of hormonal menstrual suppression in prevention of vaginal bleeding among young women who underwent hematopoietic stem cell transplantation (HCT). Retrospective descriptive study. University-based pediatric HCT practice. Fifty-five postmenarchal women who underwent HCT between 2004 and 2011. Administration of GnRH agonists or other forms of hormonal menstrual suppression. Rates of use of GnRH agonists and other forms of hormonal menstrual suppression, and rates and descriptions of vaginal bleeding. Forty-six of the 55 patients had experienced regular or irregular vaginal bleeding before HCT and were considered to be at risk for thrombocytopenia-associated menorrhagia. Forty of the 46 (87%) received hormonal menstrual suppression. Thirty-three patients were treated with a GnRH agonist, 4 with combined hormonal contraceptive pills, 1 with a combined hormonal contraceptive patch, 1 with depot medroxyprogesterone, and 1 with oral norethindrone. Twenty-nine of the 33 patients (88%) who received a GnRH agonist had complete amenorrhea during HCT and 4 of 33 (12%) experienced some degree of vaginal bleeding. GnRH agonists appear effective in prevention of vaginal bleeding complications in most postmenarchal women who underwent HCT. Some patients who might benefit do not receive a GnRH agonist and multiple barriers exist in identification and treatment of them. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  20. Gastrin induces parathyroid hormone-like hormone expression in gastric parietal cells.(RESEARCH ARTICLE / Hormones, Neurotransmitters, Growth Factors, Receptors, and Signaling)

    National Research Council Canada - National Science Library

    Demitrack, Elise S; Samuelson, Linda C; Menhali, Asma Al; Keeley, Theresa M

    2017-01-01

    ... for homeostasis of the gastric epithelium. The gastrointestinal hormone gastrin is known to be a central regulator of both parietal cell function and gastric epithelial cell proliferation and differentiation...

  1. Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Legind, Pernille; Kjelgaard-Hansen, Mads

    2014-01-01

    Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidi......, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP)....

  2. The effect of long-term prednisone treatment on growth hormone and insulin-like growth factor-1

    NARCIS (Netherlands)

    Prummel, M. F.; Wiersinga, W. M.; Oosting, H.; Endert, E.

    1996-01-01

    Due to a lack of longitudinal data the precise effect of long-term corticosteroid treatment on serum levels of the anabolic hormones Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) is unknown. Therefore, we prospectively followed GH and IGF-1 levels over a six month period in 18

  3. Hormonal Contraceptive Use as Risk Factor for Breast Cancer in Young Javanese Women

    Directory of Open Access Journals (Sweden)

    Luna Fitria Kusuma

    2017-02-01

    Full Text Available Previous study from 351 Indonesian women shown that they had breast cancers at younger age compared with western. In this study we investigate role of hormonal contraceptive as risk factor for Indonesian Javanese young breast cancer cases. However, the presence different life style between ethnic alter their risk as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, must therefore be validated in Asian women. We undertook case-control study to determine population-based distributions of breast cancer among young Javanese people, one of the largest populations in Indonesia (Southeast Asia. A total of 500 women diagnosed with breast cancer participated in this study, divided in to two group young (less 40 years old and mature breast cancer. Data for hormonal contraceptive, clinico-pathological characteristics and other risk factors were collected. We found that young Javanese women who use hormonal contraceptive for more than 10 years had a 4,67 fold increased risk of being diagnosed with breast cancer in young age (p<0,01. We didn’t found any differences between this two groups in menarche and parity. Interestingly for Javanese women who breast feeding more than 18 months increase 1,74 fold increased risk of being diagnosed with breast cancer in young age (p<0,01.

  4. Influence of environmental factors on mercury release in hydroelectric reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, K.; Therien, N.

    1991-04-01

    Due to increased mercury concentrations in fish in hydro-electric reservoirs after flooding, a study was carried out to evaluate the release and transformation of mercury due to vegetation and soil flooded as a result of reservoir creation. Samples of vegetation and soils were immersed in water and concentrations of total mercury, methylmercury and nutrients were followed. The effects of anoxia, pH and temperature on release and transformation were examined. An existing dynamic model of decomposition of flooded materials in reservoirs was modified to include mercury release and transformation, and was calibrated to the experimental data. Amounts of mercury released by the different substrates was of the same order of magnitude. Tree species contributed to the greatest amounts of methylmercury per unit biomass, but the biomass used for these was twigs and foliage. Soil released significant amounts of mercury, but methylation was very low. The model was able to fit well for all substrates except lichen. The model can be adapted to proposed reservoirs to predict nutrient and mecury release and transformation. 175 refs., 38 figs., 38 tabs.

  5. FACTORS AFFECTING THE RELEASE RATE OF A HIGHLY SOLUBLE DRUG FROM A PROGRAMMED RELEASE MEGALOPOROUS SYSTEM

    NARCIS (Netherlands)

    VANDERVEEN, C; MENGER, NR; LERK, CF

    The present study reports on the successful incorporation of a highly soluble drug, procaine HCl, in a programmed-release megaloporous system. This solid two-phase system is composed of housing phase matrix granules (HMG), controlling liquid penetration into the system, and of restraining phase

  6. Factors controlling alkali salt deposition in recovery boilers. Release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P.; Kurkela, M.; Kylloenen, H.; Tapola, E. [VTT Energy, Espoo (Finland). Process Technology Group

    1997-10-01

    The research was part of an ongoing cooperative research effort aimed at developing a model to describe the behaviour of inorganic compounds in kraft recovery boilers. During 1996 experimental investigations of sulphur release were continued. Experiments at elevated pressures and employing larger particle sizes were performed in order to gain information about mass transfer effects. The first experiments yielding data on the rates of the sulphur-release reactions were performed. This data will be used as the basis of a drop model for sulphur release being developed in cooperation with another research group. The other part of the work during 1996 explored the possibility of using chemical equilibrium calculations to predict the release of sodium, potassium and chlorine in the recovery furnace. The approach is essentially different from that employed in earlier studies in that the effects of fume formation are taken into account. So far, the predictions of the chemical equilibrium release model have, in no way, conflicted with field measurements. (orig.)

  7. Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats

    Directory of Open Access Journals (Sweden)

    Viridiana Alcántara-Alonso

    2017-10-01

    Full Text Available Individuals who consume a diet deficient in zinc (Zn-deficient develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH concentration, but unchanged thyroid hormone (TH levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII in the medial-basal hypothalamus (MBH. PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH. This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

  8. Reproductive and Hormonal Factors in Association With Ovarian Cancer in the Netherlands Cohort Study

    Science.gov (United States)

    Braem, M. G. M.; Onland-Moret, N. C.; van den Brandt, P. A.; Goldbohm, R. A.; Peeters, P. H. M.; Kruitwagen, R. F. P. M.; Schouten, L. J.

    2010-01-01

    Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian cancer among postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. Information on reproductive history and exogenous hormone use was obtained through a self-administered questionnaire at baseline in 1986. After 16.3 years of follow-up, 375 cases and 2,331 subcohort members were available for case-cohort analysis. Ovarian cancer risk was reduced for parous women, with increasing parity, and for hysterectomized women. Moreover, the authors found evidence that oral contraceptive use is protective against ovarian cancer, even when initiated at an older age. In addition, a reduced risk was observed for each year reduction in age at natural menopause and per year reduction in total menstrual life span. A small increased risk was observed with prolonged time to pregnancy, but no difference was found between ever-married nulliparous women and never-married nulliparous women. Moreover, no associations were observed for age at first birth, age at menarche, age at first and last use of oral contraceptives, and use of hormone replacement therapy. PMID:20861144

  9. Post-translational modifications of hormone-responsive transcription factors: the next level of regulation.

    Science.gov (United States)

    Hill, Kristine

    2015-08-01

    Plants exhibit a high level of developmental plasticity and growth is responsive to multiple developmental and environmental cues. Hormones are small endogenous signalling molecules which are fundamental to this phenotypic plasticity. Post-translational modifications of proteins are a central feature of the signal transduction pathways that regulate gene transcription in response to hormones. Modifications that affect the function of transcriptional regulators may also serve as a mechanism to incorporate multiple signals, mediate cross-talk, and modulate specific responses. This review discusses recent research that suggests hormone-responsive transcription factors are subject to multiple modifications which imply an additional level of regulation conferred by enzymes that mediate specific modifications, such as phosphorylation, ubiquitination, SUMOylation, and S-nitrosylation. These modifications can affect protein stability, sub-cellular localization, interactions with co-repressors and activators, and DNA binding. The focus here is on direct cross-talk involving transcription factors downstream of auxin, brassinosteroid, and gibberellin signalling. However, many of the concepts discussed are more broadly relevant to questions of how plants can modify their growth by regulating subsets of genes in response to multiple cues. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. 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.

  11. Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide.

    Science.gov (United States)

    Navarro, V M; Castellano, J M; Fernández-Fernández, R; Barreiro, M L; Roa, J; Sanchez-Criado, J E; Aguilar, E; Dieguez, C; Pinilla, L; Tena-Sempere, M

    2004-10-01

    The gonadotropic axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals that is activated at puberty. Recently, loss of function mutations of the gene encoding G protein-coupled receptor 54 (GPR54), the putative receptor for the KiSS-1-derived peptide metastin, have been associated with lack of puberty onset and hypogonadotropic hypogonadism. Yet the pattern of expression and functional role of the KiSS-1/GPR54 system in the rat hypothalamus remain unexplored to date. In the present work, expression analyses of KiSS-1 and GPR54 genes were conducted in different physiological and experimental settings, and the effects of central administration of KiSS-1 peptide on LH release were assessed in vivo. Persistent expression of KiSS-1 and GPR54 mRNAs was detected in rat hypothalamus throughout postnatal development, with maximum expression levels at puberty in both male and female rats. Hypothalamic expression of KiSS-1 and GPR54 genes changed throughout the estrous cycle and was significantly increased after gonadectomy, a rise that was prevented by sex steroid replacement both in males and females. Moreover, hypothalamic expression of the KiSS-1 gene was sensitive to neonatal imprinting by estrogen. From a functional standpoint, intracerebroventricular administration of KiSS-1 peptide induced a dramatic increase in serum LH levels in prepubertal male and female rats as well as in adult animals. In conclusion, we provide novel evidence of the developmental and hormonally regulated expression of KiSS-1 and GPR54 mRNAs in rat hypothalamus and the ability of KiSS-1 peptide to potently stimulate LH secretion in vivo. Our current data support the contention that the hypothalamic KiSS-1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood.

  12. Reproductive and hormonal risk factors of breast cancer: a historical perspective.

    Science.gov (United States)

    Horn, Julie; Vatten, Lars J

    2017-01-01

    The complexity of breast cancer etiology has puzzled scientists for more than 300 years. In this brief review, we emphasize the importance of reproductive and hormonal factors in relation to the risk of breast cancer. By following the historical course of how various risk factors have been determined, this study attempts to illustrate the origin of hypotheses, their subsequent rejection, and development of new hypotheses. Starting with the contributions of Italian physicians in the 18th century and covering the activity of British epidemiologists before World War II, this review ends up with the international collaboration that became increasingly important in the second half of the 20th century.

  13. Effects of Hypergravity Rearing on Growth Hormone and Insulin-Like Growth Factor in Rat Pups

    Science.gov (United States)

    Baer, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.

    2003-01-01

    Body weights of rat pups reared during exposure to hypergravity (hg) are significantly reduced relative to 1 g controls. In the present study, we examined in hg-reared rat pups two major contributors to growth and development, namely growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Beginning on Gestational day (G)11 of the rats 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g or 2.0-g. On Postnatal day (P)l0, plasma GH and IGF-1 were analyzed using radioimmunoassay (RIA). Both hormones were significantly elevated in hg pups relative to 1-g control pups. Together, these findings suggest that GH and IGF-1 are not primary determinants of reduced body weights observed in hg-reared pups. The significant elevations in pup GH and IGF-1 may be related to increased physical stimulation in hypergravity.

  14. Pattern of induced estrus and conception rate following Ovsynch and Ovsynch based gonadotropin-releasing hormone treatments initiated on day 6 of estrous cycle in repeat breeding crossbred cows

    National Research Council Canada - National Science Library

    Ahmed, N; Kathiresan, D; Ahmed, F A; Lalrintluanga, K; Mayengbam, P; Gali, J M

    2016-01-01

    .... This study was carried out on 24 repeat breeding crossbred cows allotted into four groups. Cows of Group I was not given any treatment, Group II was treated with gonadotropin-releasing hormone (GnRH...

  15. Characterization of Protease-Releasing Factors Isolated from Hemocytes of the Solitary Ascidian, Halocynthia roretzi

    OpenAIRE

    Kaoru, Azumi; Hideyoshi, Yokosawa; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University

    1997-01-01

    We have previously demonstrated that hemocytes of the solitary ascidian Halocynthia roretzi respond to several stimuli, such as calcium ionophore, lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), and to release metalloproteases. Here, we show that H.roretzi hemocytes contained two substances, named protease0releasing factors A and B, which induced the release of metalloproteases from the hemocytes. Factor A was isolated from the acid-ethanol extract of hemocytes by gel filt...

  16. [Puberty, pregnancy, gender and hormonal status--putative risk factors for diabetic nephropathy].

    Science.gov (United States)

    Panduru, N M; Chivu, Laura Ioana; Chivu, R D; Bădărău, Ioana Anca; Albu, D F; Fica, Simona; Ion, Daniela Adriana

    2009-01-01

    Contemplation of non-genetic risk factors that are influencing the onset and development of diabetic nephropathy (diabetic kidney disease--DKD) is very important. This article is integrative, assessing the existent data about several possible risk factors for DKD. Because the age of onset and postpubertal duration of diabetes seems to be strongly correlated with DKD, it is feasible for puberty to be another independent risk factor. Data analysis regarding puberty and possible explanatory mechanisms to link it with DKD, as the connection with DKD of other situations, with special hormonal status (like pregnancy), is also part of this article. Summing up the data about hormonal status, we can conclude that ANF levels are a risk factor for diabetic nephropathy because they are implicated in diminution of urinary Na elimination and hypertension and subsequent urinary albumin excretion (UAE) in case of inadequate glycaemic control. The evidences regarding GH are indicating that it is a risk factor for DKD and that he is probably implicated in glomerular hypertrophy onset at puberty. The urinary elimination levels of GH are very strong correlated with UAE being putative early marker for DKD. Also the GH deficiency seems to be a protective mechanism for DKD apparition. GH is strongly correlated with IGF-1 that has very high urinary levels in microalbuminuric patients. These levels are very well related to UAE, kidney volume--important markers for glomerular hypertrophy. The evidences accumulated until now regarding the role of masculine gender, testosterone and estrogens in DKD are inarticulate.

  17. Gonadotrophin-releasing hormone agonist combined with high-intensity focused ultrasound ablation for adenomyosis: a clinical study.

    Science.gov (United States)

    Guo, Y; Duan, H; Cheng, J; Zhang, Y

    2017-08-01

    This study was to investigate the clinical efficacy of a gonadotrophin-releasing hormone agonist (GnRH-a) combined with high-intensity focused ultrasound (HIFU) ablation treatment for adenomyosis. A non-randomized prospective study. Gynaecological Minimally Invasive Centre in a single hospital. Patients with adenomyosis. Seventy-nine patients with adenomyosis were enrolled, including 55 patients in the control group treated with only HIFU and 24 patients in the study group treated with GnRH-a combined with HIFU. All the patients follow up 6 months after the HIFU procedure. The related parameters in the two groups were assessed before and 3 months as well as 6 months after treatment including serum levels of tumor marker and cytokine, volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrheal scores. Differences between the group treated with HIFU alone and the group treated with GnRH-a combined with HIFU. Before HIFU treatment, no significant difference was observed in serum levels of CA125, CA19-9, and interleukin-6 (IL-6), the volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrhea scores between the two groups. (P > 0.05). The serum CA125 levels significantly decreased in both groups after HIFU, but the serum CA125 levels in the study group were still significantly lower than those in the control group (P HIFU procedure, and decreased even more in the study group 3 and 6 months after treatment (P HIFU treatment. Moreover in the study group were significantly lower than those in the control group after 3 and 6 months (P HIFU treatment significantly decreased serum CA125 levels, volumes of uterine, adenomyotic lesion and menstrual blood, as well as dysmenorrhea scores, and improved the clinical outcomes compared with the HIFU ablation alone in patients with adenomyosis. However, the further follow-up is needed to explore the long-term effects. A combination of GnRH-a with HIFU in the treatment of

  18. Effect of Antiandrogen, Aromatase Inhibitor, and Gonadotropin-releasing Hormone Analog on Adult Height in Familial Male Precocious Puberty.

    Science.gov (United States)

    Leschek, Ellen Werber; Flor, Armando C; Bryant, Joy C; Jones, Janet V; Barnes, Kevin M; Cutler, Gordon B

    2017-11-01

    Antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog (GnRHa) treatment normalizes growth rate and bone maturation and increases predicted adult height (AH) in boys with familial male-limited precocious puberty (FMPP). To evaluate the effect of long-term antiandrogen, aromatase inhibitor, and GnRHa on AH, boys with FMPP who were treated were followed to AH. Twenty-eight boys with FMPP, referred to the National Institutes of Health, were started on antiandrogen and aromatase inhibitor at 4.9 ± 1.5 years of age; GnRHa was added at 6.9 ± 1.5 years of age. Treatment was discontinued at 12.2 ± 0.5 years of age (bone age, 14.4 ± 1.3). AH was assessed at 16.4 ± 1.3 years of age (bone age, 18.5 ± 0.6). AH (mean ± SD) for all treated subjects was 173.6 ± 6.8 cm (-0.4 ± 1.0 SD relative to adult US males). For 25 subjects with pretreatment predicted AH, AH significantly exceeded predicted AH at treatment onset (173.8 ± 6.9 vs 164.9 ± 10.7 cm; P < .001), but fell short of predicted AH at treatment discontinuation (177.3 ± 9.0 cm; P < .001). For 11 subjects with maternal or sporadic inheritance, the mean AH was 3.1 cm (0.4 SD score) below sex-adjusted midparental height (175.4 ± 5.8 vs 178.5 ± 3.1 cm [midparental height]; P = .10). For 16 subjects with affected and untreated fathers, AH was significantly greater than fathers' AH (172.8 ± 7.4 vs 168.8 ± 7.2 cm; P < .05). Long-term treatment with antiandrogen, aromatase inhibitor, and GnRHa in boys with FMPP results in AH modestly below sex-adjusted midparental height and within the range for adult males in the general population. Published by Elsevier Inc.

  19. Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Kyle D. Ketchesin

    2017-10-01

    Full Text Available Corticotropin-releasing hormone-binding protein (CRH-BP is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC. Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT or glutamic acid decarboxylase (GAD mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85% between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV, somatostatin (SST, vasoactive intestinal peptide (VIP and cholecystokinin (CCK. We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type-specific manner to better

  20. Functional Characterization of Paralogous Gonadotropin-Releasing Hormone-Type and Corazonin-Type Neuropeptides in an Echinoderm

    Science.gov (United States)

    Tian, Shi; Egertová, Michaela; Elphick, Maurice R.

    2017-01-01

    Homologs of the vertebrate neuropeptide gonadotropin-releasing hormone (GnRH) have been identified in invertebrates, including the insect neuropeptide corazonin (CRZ). Recently, we reported the discovery of GnRH-type and CRZ-type signaling systems in an echinoderm, the starfish Asterias rubens, demonstrating that the evolutionary origin of paralogous GnRH-type and CRZ-type neuropeptides can be traced back to the common ancestor of protostomes and deuterostomes. Here, we have investigated the physiological roles of the GnRH-type (ArGnRH) and the CRZ-type (ArCRZ) neuropeptides in A. rubens, using mRNA in situ hybridization, immunohistochemistry and in vitro pharmacology. ArGnRH precursor (ArGnRHP)-expressing cells and ArGnRH-immunoreactive cells and/or processes are present in the radial nerve cords, circumoral nerve ring, digestive system (e.g., cardiac stomach and pyloric stomach), body wall-associated muscle (apical muscle), and appendages (tube feet, terminal tentacle). The general distribution of ArCRZ precursor (ArCRZP)-expressing cells is similar to that of ArGnRHP, but with specific local differences. For example, cells expressing ArGnRHP are present in both the ectoneural and hyponeural regions of the radial nerve cords and circumoral nerve ring, whereas cells expressing ArCRZP were only observed in the ectoneural region. In vitro pharmacological experiments revealed that both ArGnRH and ArCRZ cause contraction of cardiac stomach, apical muscle, and tube foot preparations. However, ArGnRH was more potent/effective than ArCRZ as a contractant of the cardiac stomach, whereas ArCRZ was more potent/effective than ArGnRH as a contractant of the apical muscle. These findings demonstrate that both ArGnRH and ArCRZ are myoexcitatory neuropeptides in starfish, but differences in their expression patterns and pharmacological activities are indicative of distinct physiological roles. This is the first study to investigate the physiological roles of both GnRH-type and

  1. Functional Characterization of Paralogous Gonadotropin-Releasing Hormone-Type and Corazonin-Type Neuropeptides in an Echinoderm

    Directory of Open Access Journals (Sweden)

    Shi Tian

    2017-09-01

    Full Text Available Homologs of the vertebrate neuropeptide gonadotropin-releasing hormone (GnRH have been identified in invertebrates, including the insect neuropeptide corazonin (CRZ. Recently, we reported the discovery of GnRH-type and CRZ-type signaling systems in an echinoderm, the starfish Asterias rubens, demonstrating that the evolutionary origin of paralogous GnRH-type and CRZ-type neuropeptides can be traced back to the common ancestor of protostomes and deuterostomes. Here, we have investigated the physiological roles of the GnRH-type (ArGnRH and the CRZ-type (ArCRZ neuropeptides in A. rubens, using mRNA in situ hybridization, immunohistochemistry and in vitro pharmacology. ArGnRH precursor (ArGnRHP-expressing cells and ArGnRH-immunoreactive cells and/or processes are present in the radial nerve cords, circumoral nerve ring, digestive system (e.g., cardiac stomach and pyloric stomach, body wall-associated muscle (apical muscle, and appendages (tube feet, terminal tentacle. The general distribution of ArCRZ precursor (ArCRZP-expressing cells is similar to that of ArGnRHP, but with specific local differences. For example, cells expressing ArGnRHP are present in both the ectoneural and hyponeural regions of the radial nerve cords and circumoral nerve ring, whereas cells expressing ArCRZP were only observed in the ectoneural region. In vitro pharmacological experiments revealed that both ArGnRH and ArCRZ cause contraction of cardiac stomach, apical muscle, and tube foot preparations. However, ArGnRH was more potent/effective than ArCRZ as a contractant of the cardiac stomach, whereas ArCRZ was more potent/effective than ArGnRH as a contractant of the apical muscle. These findings demonstrate that both ArGnRH and ArCRZ are myoexcitatory neuropeptides in starfish, but differences in their expression patterns and pharmacological activities are indicative of distinct physiological roles. This is the first study to investigate the physiological roles of both Gn

  2. Co-localization of three gonadotropin-releasing hormone transcripts in larval, parasitic, and adult sea lamprey brains.

    Science.gov (United States)

    Van Gulick, Emily R; Marquis, Timothy J; Sower, Stacia A

    2017-08-03

    RNA expression of lamprey gonadotropin-releasing hormone (lGnRH)-I, -II, and -III was demonstrated in the brains of larval, parasitic phase and adult sea lampreys, Petromyzon marinus, using a highly sensitive triple-label in situ hybridization technique. In female larval lampreys, lGnRH-I and-II were co-expressed in the same neurons throughout the olfactory bulbs, preoptic area (POA), and rhombencephalon (hindbrain); lGnRH-I, -II and -III were triple co-expressed in the hypothalamus and in the paranuclear region of neuronal somas in the rhombencephalon. In female parasitic phase lampreys, lGnRH-I and -II were co-expressed in the POA, thalamus, and preoptico-neurohypophyseal tract (PNT); lGnRH-III was minimally triple co-expressed with lGnRH-I and -II in the hypothalamus. In adult female lampreys, lGnRH-I and -III were co-expressed in the hypothalamus; lGnRH-I was also expressed in the neurohypophysis (NH). In adult male lampreys, lGnRH-I and-III were co-expressed in the primordial hippocampus, POA, thalamus, hypothalamus, NH, and PNT; lGnRH-I was also expressed in the epithalamus. In summary, we provide the first study using in situ hybridization of all three lGnRHs (lGnRH-I, -II, and -III) at three major life stages (larval, parasitic, and adult) of lampreys, which strongly supports previous immunohistological studies and suggests that lGnRH-I and -II are the predominant lGnRHs in larval and parasitic phase lampreys, and that lGnRH-I and -III are the predominant lGnRHs in adult female and male lampreys. Therefore, our results show that lGnRH-I, -II, and -III have different localization and co-expression in the development and sexual maturation of lampreys, which may suggest unique physiological roles at each life stage and sex in the developing and mature lamprey brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility.

    Science.gov (United States)

    Park, Hyun Jun; Koo, Yean Kyoung; Park, Min Jung; Hwang, Yoon Kyung; Hwang, Sung Yeoun; Park, Nam Cheol

    2017-10-25

    We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were estimated. Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model.

  4. 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 peptide...... and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism....

  5. Changes in cardiovascular risk factors and hormones during a comprehensive residential three month kriya yoga training and vegetarian nutrition.

    Science.gov (United States)

    Schmidt, T; Wijga, A; Von Zur Mühlen, A; Brabant, G; Wagner, T O

    1997-01-01

    In participants of a comprehensive residential three month yoga and mediation training programme living on a low fat lacto-vegetarian diet changes in cardiovascular risk factors and hormones were studied. Substantial risk factor reduction was found. Body mass index, total serum and LDL cholesterol, fibrinogen, and blood pressure were significantly reduced especially in those with elevated levels. Urinary excretion of adrenaline, noradrenaline, dopamine, aldosterone, as well as serum testosterone and luteinizing hormone levels were reduced, while cortisol excretion increased significantly.

  6. Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

    Science.gov (United States)

    Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

    2012-01-01

    Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (padult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (padult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (pincreased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone. PMID:23926409

  7. An aggregated analysis of hormonal factors and endometrial cancer risk by parity.

    Science.gov (United States)

    Schonfeld, Sara J; Hartge, Patricia; Pfeiffer, Ruth M; Freedman, D Michal; Greenlee, Robert T; Linet, Martha S; Park, Yikyung; Schairer, Catherine; Visvanathan, Kala; Lacey, James V

    2013-04-01

    Nulliparity is associated with an increased risk of endometrial cancer. It is less clear whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies to date have been too small to test the hypothesis that endometrial cancer risk factors may be associated more strongly with risk among nulliparous women compared with parous women. Data were aggregated on 26,936 postmenopausal, Caucasian, nulliparous women (360 endometrial cancers) and 146,583 postmenopausal, Caucasian, parous women (1378 endometrial cancers) from 4 US prospective studies (1979-2006). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in stratified analyses. The risk of endometrial cancer was higher among nulliparous women than among parous women, as expected (nulliparous vs parous: HR, 1.42; 95% CI, 1.26-1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ between nulliparous versus parous women: For both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity: A body mass index ≥30 kg/m(2) (vs endometrial cancer 3-fold among nulliparous women (HR, 3.04; 95% CI, 2.34-3.94) and parous women (HR, 2.88; 95% CI, 2.52-3.29). The results from this large, pooled analysis of data from 4 large prospective studies suggested that nulliparity does not modify the risks of endometrial cancer associated with established hormone-related risk factors. Copyright © 2012 American Cancer Society.

  8. An Aggregated Analysis of Hormonal Factors and Endometrial Cancer Risk by Parity

    Science.gov (United States)

    Schonfeld, Sara J.; Hartge, Patricia; Pfeiffer, Ruth M.; Freedman, D. Michal; Greenlee, Robert T.; Linet, Martha S.; Park, Yikyung; Schairer, Catherine; Visvanathan, Kala; Lacey, JV

    2013-01-01

    Background Nulliparity is associated with an increased risk of endometrial cancer. Less clear is whether nulliparity modifies the association between other established hormone-related risk factors. The proportion of nulliparous women has increased since the mid-1970s, but most individual studies are too small to test the hypothesis that endometrial cancer risk factors may be more strongly associated with risk among nulliparous women compared with parous women. Methods We aggregated data on 26,936 postmenopausal, Caucasian nulliparous women (360 endometrial cancers) and 146,583 postmenopausal Caucasian parous women (1,378 endometrial cancers) from four U.S. prospective studies (1979–2006). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) in stratified analyses. Results As expected, endometrial cancer risk was higher among nulliparous women than among parous women (HR, nulliparous vs. parous = 1.42, 95% CI 1.26 to 1.60). Stratified associations between endometrial cancer and hormone-related risk factors did not differ among nulliparous vs. parous women: among both groups, oral contraceptives and earlier menopause were associated with reduced risk. The highest HRs were for obesity; body mass index ≥30 kg/m2 (vs. endometrial cancer risk three-fold among nulliparous (HR= 3.04, 95% CI 2.34 to 3.94) and parous (HR= 2.88, 95% CI 2.52 to 3.29) women. Conclusions The results from this large, pooled analysis of data from four large prospective studies suggest that nulliparity does not modify endometrial cancer risks associated with established hormone-related risk factors. PMID:23280123

  9. Subarachnoid hemorrhage and hormonal factors in women. A population-based case-control study.

    Science.gov (United States)

    Longstreth, W T; Nelson, L M; Koepsell, T D; van Belle, G

    1994-08-01

    To determine the degree to which endogenous and exogenous hormonal factors influence the risk for subarachnoid hemorrhage in women. A population-based case-control study. King County, Washington. 103 women with an incident, spontaneous subarachnoid hemorrhage and 2 age- and sex-matched controls per case-patient who were identified through random-digit dialing. Information on exposures was collected during in-person interviews of case-patients, controls, and their surrogates. Premenopausal women, especially those without a history of smoking or hypertension, were at a reduced risk for subarachnoid hemorrhage compared with age-matched postmenopausal women (odds ratio, 0.24; 95% CI, 0.09 to 0.68). The use of hormone replacement therapy was associated with a reduced risk (odds ratio, 0.47; CI, 0.26 to 0.86); the reduction was significantly greater in women who had smoked than in those that had never smoked. Of the 23 premenopausal case-patients, 74% were either menstruating when hemorrhaging occurred or had had their last menstrual period 21 or more days before hemorrhaging compared with the expected 43% (difference, 31%; CI, 4% to 58%). Premenopausal women are at reduced risk for subarachnoid hemorrhage, especially those without a history of smoking or hypertension. Hormone replacement therapy reduced the risk only in postmenopausal women who had ever smoked. Among women still menstruating, the risk for hemorrhage was greatest in the perimenstrual period.

  10. MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP induced corticotropin releasing hormone (CRH expression in JEG3 choriocarcinoma cell line

    Directory of Open Access Journals (Sweden)

    Kocak Hande

    2009-07-01

    Full Text Available Abstract Background Classically protein kinase A (PKA and transcription factor activator protein 1 (AP-1 mediate the cyclic AMP (cAMP induced-corticotrophin releasing hormone (CRH expression in the placenta. However enteric Gram (- bacterial cell wall component lipopolysaccharide (LPS may also induce-CRH expression via Toll like receptor (TLR4 and its adaptor molecule Myd88. Here we investigated the role of MyD88, TRIF and IRAK2 on cAMP-induced CRH promoter activation in JEG3 cells in the absence of LPS/TLR4 stimulation. Methods JEG3 cells were transfected with CRH-luciferase and Beta-galactosidase expression vectors and either empty or dominant-negative (DN-MyD88, DN-TRIF or DN-IRAK2 vectors using Fugene6 (Roche. cAMP-induced CRH promoter activation was examined by using a luminometer and luciferase assay. Calorimetric Beta-galactosidase assays were performed to correct for transfection efficiency. Luciferase expression vectors of cAMP-downstream molecules, CRE and AP-1, were used to further examine the signaling cascades. Results cAMP stimulation induced AP-1 and CRE promoter expression and led to dose-dependent CRH promoter activation in JEG3 cells. Inhibition of MyD88 signaling blocked cAMP-induced CRE and CRH promoter activation. Inhibition of TRIF signaling blocked cAMP-induced CRH but not CRE expression, while inhibition of IRAK2 did not have an effect on cAMP-induced CRH expression. Conclusion MyD88 and TRIF exert direct regulatory effect on cAMP-induced CRH promoter activation in JEG3 cells in the absence of infection. MyD88 most likely interacts with molecules upstream of IRAK2 to regulate cAMP-induced CRH expression.

  11. Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide

    Science.gov (United States)

    Pérez Sirkin, Daniela I.; Lafont, Anne-Gaëlle; Kamech, Nédia; Somoza, Gustavo M.; Vissio, Paula G.; Dufour, Sylvie

    2017-01-01

    GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D) structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH), despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH) structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation. PMID:28878737

  12. A Critical Appraisal of the Effect of Gonadotropin-Releasing Hormon Analog Treatment on Adult Height of Girls with Central Precocious Puberty.

    Science.gov (United States)

    Bereket, Abdullah

    2017-12-30

    Central precocious puberty (CPP) is a diagnosis that pediatric endocrinologists worldwide increasingly make in girls of age 6-8 years and is mostly idiopathic. Part of the reason for increasing referral and diagnosis is the perception among the doctors as well as the patients that treatment of CPP with long-acting gonadotropin-releasing hormon analogues (GnRHa) promote height of the child. Although, the timing and the tempo of puberty does influence statural growth and achieved adult height, the extent of this effect is variable depending on several factors and is modest in most cases. Studies investigating GnRHa treatment in girls with idiopathic CPP demonstrate that treatment is able to restore adult height compromised by precocious puberty. However, reports on untreated girls with precocious puberty demonstrate that some of these girls achieve their target height without treatment as well, thus, blurring the net effect of GnRHa treatment on height in girls with CPP. Clinical studies on treatment of girls with idiopathic CPP on adult stature suffers from the solid evidence-base due mainly to the lack of well-designed randomized controlled studies and our insufficiencies of predicting adult height of a child with narrow precision. This is particularly true for girls in whom age of pubertal onset is close to physiological age of puberty, which are the majority of cases treated with GnRHa nowadays. Heterogeneous nature of pubertal tempo (progressive vs. nonprogressive) leading to different height outcomes also complicates the interpretation of the results in both treated and untreated cases. This review will attemp to summarize and critically appraise available data in the field.

  13. Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study.

    Science.gov (United States)

    Costarelli, Laura; Giacconi, Robertina; Malavolta, Marco; Basso, Andrea; Piacenza, Francesco; DeMartiis, MariLuisa; Giannandrea, Elvio; Renieri, Carlo; Busco, Franco; Galeazzi, Roberta; Mocchegiani, Eugenio

    2014-06-01

    Zinc is a relevant nutritional factor for the whole life of an organism because it affects the inflammatory/immune response and antioxidant activity, leading to a healthy state. Despite its important function, the dietary intake of zinc is inadequate in elderly. Possible interventions include food fortification because it does not require changes in dietary patterns, the cost is low and it can reach a large portion of the elderly population, including very old subjects. Studies evaluating the impact of Zn-fortified foods on functional parameters in elderly, in particular, in very old individuals, are missing. The objective of this study was to evaluate the efficacy of consumption of a zinc-fortified drinking skim milk (Zn-FMilk) for a period of 2 months in comparison to standard non-fortified milk (No-FMilk) on some biochemical parameters, zinc status, inflammatory/immune response and on a key parameter of the T cell-mediated immunity (thymulin hormone) in healthy very old subjects. The treatment with zinc-fortified milk (Zn-FMilk) is a good omen to increase the cell-mediated immunity in very old age represented by thymulin activity and some cytokine (IL-12p70, IFN-γ) release. At clinical level, a good healthy state occurs in 70 % of the subjects with no hospitalization after 1 year of the follow-up in comparison to very old control subjects that did not participate to crossover design. In conclusion, the Zn-FMilk can be considered a good functional food for elderly, including older people. It might be a good replacement to the zinc tablets or lozenges taking into account the attitude of old people to uptake milk as a preferential food.

  14. Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

    Science.gov (United States)

    Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

    2009-01-01

    Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

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

    Directory of Open Access Journals (Sweden)

    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 cys