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Sample records for leuteinizing hormone-releasing hormone

  1. Familial growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism.

    OpenAIRE

    Stirling, H F; Barr, D G; Kelnar, C J

    1991-01-01

    A mother with pseudopseudohypoparathyroidism and her short son showed poor spontaneous growth hormone secretion, and provocation tests suggested a deficiency of growth hormone releasing factor. This is the first report of growth hormone releasing factor deficiency in pseudopseudohypoparathyroidism. The boy has responded well to growth hormone treatment over a period of three years.

  2. Metabolism of growth hormone releasing peptides.

    Science.gov (United States)

    Thomas, Andreas; Delahaut, Philippe; Krug, Oliver; Schänzer, Wilhelm; Thevis, Mario

    2012-12-04

    New, potentially performance enhancing compounds have frequently been introduced to licit and illicit markets and rapidly distributed via worldwide operating Internet platforms. Developing fast analytical strategies to follow these new trends is one the most challenging issues for modern doping control analysis. Even if reference compounds for the active drugs are readily obtained, their unknown metabolism complicates effective testing strategies. Recently, a new class of small C-terminally amidated peptides comprising four to seven amino acid residues received considerable attention of sports drug testing authorities due to their ability to stimulate growth hormone release from the pituitary. The most promising candidates are the growth hormone releasing peptide (GHRP)-1, -2, -4, -5, -6, hexarelin, alexamorelin, and ipamorelin. With the exemption of GHRP-2, the entity of these peptides represents nonapproved pharmaceuticals; however, via Internet providers, all compounds are readily available. To date, only limited information on the metabolism of these substances is available and merely one metabolite for GHRP-2 is established. Therefore, a comprehensive in vivo (po and iv administration in rats) and in vitro (with human serum and recombinant amidase) study was performed in order to generate information on urinary metabolites potentially useful for routine doping controls. The urine samples from the in vivo experiments were purified by mixed-mode cation-exchange solid-phase extraction and analyzed by ultrahigh-performance liquid chromatography (UHPLC) separation followed by high-resolution/high-accuracy mass spectrometry. Combining the high resolution power of a benchtop Orbitrap mass analyzer for the first metabolite screening and the speed of a quadrupole/time-of-flight (Q-TOF) instrument for identification, urinary metabolites were screened by means of a sensitive full scan analysis and subsequently confirmed by high-accuracy product ion scan experiments. Two

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

    OpenAIRE

    PERONI, CIBELE N.; Cesar Y. Hayashida; Nancy Nascimento; LONGUINI, VIVIANE C.; Toledo, Rodrigo A.; Paolo Bartolini; 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/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormone-receptors, were compared to those ...

  4. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin (cis-diamminedichloroplatinum(II)) and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  5. Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

    Directory of Open Access Journals (Sweden)

    A.-M.J. Lengyel

    2006-08-01

    Full Text Available Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a discovery of this peptide, b mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c regulation of growth hormone release in man after intravenous administration of these peptides.

  6. GH responses to growth hormone releasing factor in depression.

    Science.gov (United States)

    Thomas, R; Beer, R; Harris, B; John, R; Scanlon, M

    1989-01-01

    The growth hormone (GH), thyrotrophin (TSH) and prolactin response to growth hormone releasing factor (GRF) was investigated in 18 patients suffering from major depression with melancholia and in 18 age- and sex-matched normal controls. There was no significant difference in the GH response to GRF stimulation between the patients and controls and in neither subject group was there a demonstrable TSH or prolactin response to GRF. These findings indicate that the pathophysiology underlying the blunted GH response to pharmacological challenge, demonstrated in other studies, must lie at a suprapituitary level.

  7. Luteinizing hormone-releasing hormone receptor antagonist may reduce postmenopausal flushing

    NARCIS (Netherlands)

    Gastel, P. van; Zanden, M. van der; Telting, D.; Filius, M.; Bancsi, L.; Boer, H. de

    2012-01-01

    OBJECTIVE: Hormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone-releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP

  8. Algorithmic complexity of growth hormone release in humans.

    Science.gov (United States)

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  9. Algorithmic complexity of growth hormone release in humans

    Energy Technology Data Exchange (ETDEWEB)

    Prank, K.; Wagner, M.; Brabant, G. [Medical School Hannover (Germany)

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  10. contribution of growth hormone-releasing hormone and ...

    African Journals Online (AJOL)

    hormone (GHRH) and increased somatostatin secretion to this phenomenon. ... negative feedback effects of IGF-1 or combinations of these factors. Studies to ..... increase in lean body mass and reduction in adipose tissue.6. Reduced GH ...

  11. Stimulation of chicken growth hormone release by phorbol esters.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1990-11-01

    Synergism between thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) has been shown in a primary (48 hr) culture of chicken adenohypophyseal cells established in this laboratory. The purpose of the present study was to determine if phorbol esters acting alone or in concert with TRH or hpGRF affect chicken GH release. Collagenase-dissociated chicken adenohypophyseal cells were treated (2 hr) with combinations of TRH, hpGRF, phorbol esters (activators of protein kinase C; PKC), and pharmacologic agents that increase cAMP. Phorbol myristate acetate (PMA) or phorbol dibutyrate (PDBu) alone stimulated GH release in a dose-dependent manner; either phorbol ester (10(-6) M) increased GH release from 100 to 390% over the value obtained in the absence of test agents (control). Similarly, hpGRF (10(-9) M), 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX, 10(-3) M) alone elevated GH release by at least 60% over the control value. The combined effects of phorbol esters (either PMA or PDBu) and hpGRF, 8 Br-cAMP, or forskolin on GH release were additive. Only one combination, phorbol esters with IBMX, exerted synergistic effects on GH release. No synergy was shown between TRH (1.3 x 10(-9) M) and either phorbol ester. These findings are the first to implicate PKC in chicken GH release in vitro. In addition, these studies, together with previous results, suggest that TRH and hpGRF synergy occurs via a pathway that arises prior to activation of PKC.

  12. Acceleration of wound healing by growth hormone-releasing hormone and its agonists

    OpenAIRE

    Dioufa, Nikolina; Schally, Andrew V.; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L.; Owens, Gary K.; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-01-01

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). ...

  13. 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-transgenic m......-transgenic mice, 16 to 24 months of age, develop pituitary mammosomatotroph adenomas. These findings provide conclusive evidence that protracted stimulation of secretory activity can cause proliferation, hyperplasia and adenoma of adenohypophysial cells....

  14. Dopaminergic regulation of luteinizing hormone-releasing hormone release at the median eminence level: immunocytochemical and physiological evidence in hens.

    Science.gov (United States)

    Contijoch, A M; Gonzalez, C; Singh, H N; Malamed, S; Troncoso, S; Advis, J P

    1992-03-01

    Theoretically, the most effective inhibitory control of hypophysiotropic luteinizing hormone-releasing hormone (LHRH) release might occur through a presynaptic inhibition of LHRH neuronal terminals at the median eminence (ME) level. Since: (a) we have recently reported the existence of synaptic contacts between dopamine- and LHRH-containing processes in the ewe ME, and (b) nutritional deprivation induces an ovulatory failure in both birds and mammals, we have assessed the possibility that the anovulatory state induced by feed withdrawal (FW) in laying hens, might be caused by a dopaminergic inhibition of LHRH release at the ME level. Laying hens at the start (35 weeks old) and end (75 weeks old) of their commercial egg-laying life were killed at 0, 1, 2 and 4 days after FW. Serum luteinizing hormone (LH) and progesterone (P4), in vitro release of LHRH by isolated ME, and LHRH content in ME and preoptic area (POA) were determined by RIA. ME content of dopamine (DA) and its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were assessed by LCED. The distribution of LHRH and tyrosine hydroxylase (TH)-containing processes at the ME level of the hen was determined immunocytochemically. In the hen, LHRH-containing cell bodies are localized in the anterior hypothalamus and medial POA. LHRH-containing axons project toward the ME and infundibulum through the ventral-lateral hypothalamus. TH-containing perikarya are concentrated in the arcuate nucleus and in the adjacent part of the periventricular nucleus, dorsal to the arcuate. TH-containing axons converge toward the ME and descend into the infundibulum. Dense concentrations of TH- and LHRH-containing processes are located in the lateral and mediobasal portions of the external layer of the ME, providing opportunities for synaptic interactions between them. Ovulatory failure and regression of the ovary and reproductive tract occurred 2-3 days after FW at the end, but not at the beginning of the hen's commercial egg

  15. Growth hormone-releasing hormone stimulates cAMP release in superfused rat pituitary cells.

    OpenAIRE

    Horváth, J E; Groot, K. de; Schally, A V

    1995-01-01

    The release of growth hormone (GH) and cAMP was studied in superfused rat pituitary cells by infusing growth hormone-releasing hormone (GHRH) at different doses or a combination of GHRH and somatostatin 14 (SS-14). Three-minute pulses of GHRH caused a dose-dependent GH and cAMP release (effective concentration of 50% of the maximal biological effect is 0.21 nM and 52.5 nM, respectively). The lowest effective doses of GHRH in the superfusion system were 0.03 nM for GH release and 0.3 nM for cA...

  16. 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...

  17. Active immunization to luteinizing hormone releasing hormone to inhibit the induction of mammary tumors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Ravdin, P.M.; Jordan, V.C.

    1988-01-01

    Immunization of female rats with a bovine serum albumin-luteinizing hormone releasing hormone conjugate results in suppression of dimethylbenzanthracene mammary tumor incidence. Tumor incidence was 1.3, and 1.29 tumors per rat in bovine serum albumin alone (n = 10) and unimmunized (n = 18) control groups, but no tumors were found in the bovine serum albumin-luteinizing hormone releasing hormone conjugate immunized animals (n = 10). In a second experiment immunization with bovine serum albumin-luteinizing hormone releasing hormone conjugates reduced tumor incidence to 0.3 tumors per rat (n = 10) from the 1.2 tumors per animal seen in the control animals (n = 10) immunized with bovine serum albumin alone. Bovine serum albumin-luteinizing hormone immunization caused the production of anti-LHRH antibodies, an interruption of estrous cycles, lowered serum estradiol and progesterone levels, and atrophy of the ovaries and uteri. Immunization BSA-hormone conjugates is a novel anti-tumor strategy.

  18. Long-term effects of human growth hormone-releasing hormone and photoperiod on hormone release and puberty in dairy heifers.

    Science.gov (United States)

    Ringuet, H; Pelletier, G; Brazeau, P; Gaudreau, P; Guilbault, L A; Morisset, J; Couture, Y; Petitclerc, D

    1994-10-01

    Forty-eight Holstein dairy heifers (98.9 kg BW; 3 mo old) were subjected for 246 d to twice-daily s.c. injections of saline (CTL) or human growth hormone-releasing hormone (GRH; 5 micrograms/kg BW) and to photoperiods of 8 h of light (L): 16 h of dark (D) or 16L:8D according to a 2 x 2 factorial arrangement of treatments. Jugular blood samples were collected from 16 heifers at 3, 4, 8, and 11 mo of age to monitor prolactin, growth hormone, and estradiol-17 beta. Plasma progesterone concentrations were monitored weekly in all heifers as an index of puberty (> 1 ng/mL). Growth hormone release was induced by GRH (P GRH heifers. However, GRH-induced GH response was less (P GRH, photoperiod, and days of treatment on GRH-induced GH response; AUC was greater in GRH-16L:8D than in GRH-8L:16D heifers at 3 mo but less at 8 mo of age. The PRL concentrations were similar for both photoperiods at 3 mo (36.4 vs 41.7 ng/mL) and 8 mo (16.2 vs 12.8 ng/mL) of age but were greater in 16L:8D vs 8L:16D heifers at 4 mo (18.4 vs 39.3 ng/mL) and 11 mo (26.3 vs 44.1 ng/mL) of age (photoperiod x day interaction, P GRH-treated heifers (271 vs 284 kg BW; GRH x photoperiod interaction, P = .10). In conclusion, GH response is maintained throughout 8 mo of GRH treatment, and a 16L:8D photoperiod will reduce age and weight at puberty in heifers. Furthermore, refractoriness to photoperiod-induced PRL changes was detected.

  19. Action of luteinizing hormone-releasing hormone in rat ovarian cells: Hormone production and signal transduction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian.

    1989-01-01

    The present study was conducted to investigate the hypothesis that the breakdown of membrane phosphoinositides may participate in the actions of luteinizing hormone-releasing hormone (LHRH) on hormone production in rat granulosa cells. In cells prelabeled with ({sup 3}H)inositol or ({sup 3}H)arachidonic acid (AA), treatment with LHRH increased the formation of radiolabeled inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol (DG), and the release of radiolabeled AA. Since IP{sub 3} induces intracellular Ca{sup 2+} mobilization, changes in the cytosolic free calcium ion concentrations ((Ca{sup 2+})i) induced by LHRH were studied in individual cells using fura-2 microspectrofluorimetry. Alterations in (Ca{sup 2+})i induced by LHRH were rapid and transient, and could be completely blocked by a LHRH antagonist. Sustained perifusion of LHRH resulted in a desensitization of the (Ca{sup 2+})i response to LHRH. LHRH treatment accelerated (Ca{sup 2+})i depletion in the cells perifused with Ca{sup 2+} free medium, indicating the involvement of intracellular Ca{sup 2+} pool(s) in (Ca{sup 2+})i changes. The actions of LHRH on the regulation of progesterone (P{sub 4}) and prostaglandin E{sub 2} (PGE{sub 2}) production were also examined. LHRH increased basal P{sub 4} production and attenuated FSH induced P{sub 4} production. Both basal and FSH stimulated PGE{sub 2} formation were increased by LHRH. Since LHRH also increased the formation of DG that stimulates the activity of protein kinase C, an activator of protein kinase C (12-0-tetradecanolyphorbol-13-acetate: TPA) was used with the Ca{sup 2+} ionophore A23187 and melittin (an activator of phospholipase A{sub 2}) to examine the roles of protein kinase C, Ca{sup 2+} and free AA, respectively, in LHRH action.

  20. Luteinizing hormone-releasing hormone induces thyroxine release together with testosterone in the neotenic axolotl Ambystoma mexicanum.

    Science.gov (United States)

    Jacobs, G F; Kühn, E R

    1988-09-01

    In male neotenic axolotls Ambystoma mexicanum plasma concentrations of thyroxine (T4) and testosterone were increased following intravenous injection of 10 micrograms luteinizing hormone-releasing hormone. A dose of 50 micrograms influenced only plasma T4 levels. This observation suggests for the first time that a hypothalamic hormone is capable of stimulating the thyroidal axis in the neotenic axolotl.

  1. effect of luteinizing hormone-releasing hormone analogue on the sexual behavior of sacalia quadriocellata

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    luteinizing hormone-releasing hormone (lhrh) is known to influence sexual behavior in many vertebrate taxa,but there have been no systematic studies on the role of lhrh in sexual behavior of turtles.we tested the hypotheses that exogenous lhrh analogues would induce sexual behavior of male four-eyed turtle,sacalia quadriocellata.we examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue (lhrh-a),human chorionic gonadotropin (hcg),or a combination of the two,and subsequently exposing them to sexually receptive females for behavioral observation.our data show that the injection of only hcg could not,while that of only lhrh-a could,facilitate sexual behavior along with testicular recrudescence and spermatogenesis in s.quadriocellata.the injection of both lhrh-a and hcg would induce more drastic sexual behavior of the animals than that of lhrh-a alone,indicating hcg enhances the effects of lhrh-a induced sexual behavior.however,different pharmacological dosages of lhrh-a (0.5 μg,1 μg,2 μg per 100 g bodyweight) did not correspond to different activity levels.though the mechanism of lhrh effect was not determined,this study may support that the sexual behavior ofs.quadriocellata which occurs at the beginning of the injection despite regression of the gonads.this is the first report on the exogenous lhrh-a induced sexual behavior for this species.

  2. Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells.

    OpenAIRE

    Gick, G G; Zeytin, F N; BRAZEAU, P.; Ling, N C; Esch, F S; Bancroft, C

    1984-01-01

    A peptide with high intrinsic activity for specifically stimulating the secretion of immunoreactive growth hormone (GH; somatotropin) has been characterized and reproduced by total synthesis. This peptide, human pancreatic growth hormone-releasing factor, 44-amino-acid form (hpGRF1-44-NH2), was isolated from a tumor localized in the pancreas of a patient with acromegaly. We report here the effect of this growth hormone-releasing factor (GRF) on GH release and the GH mRNA levels in monolayer c...

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Guillaume Osterstock

    Full Text Available BACKGROUND: 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. PRINCIPAL FINDINGS: 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. CONCLUSION: 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.

  5. Mouse hypothalamic growth hormone-releasing hormone and somatostatin responses to probes of signal transduction systems.

    Science.gov (United States)

    Sato, M; Downs, T R; Frohman, L A

    1993-01-01

    Signal transduction mechanisms involved in mouse growth hormone-releasing hormone (GRH) and somatostatin (SRIH) release were investigated using an in vitro perifusion system. Hypothalamic fragments were exposed to depolarizing agents, protein kinase A and C activators, and a calcium ionophore. The depolarizing agents, KCl (60 mM) and veratridine (50 microM), induced similar patterns of GRH and SRIH release. Somatostatin release in response to both agents was twofold greater than that of GRH. Forskolin (10 microM and 100 microM), an adenylate cyclase activator, stimulated both GRH and SRIH release, though with different secretory profiles. The SRIH response was prolonged and persisted beyond removal of the drug from the system, while the GRH response was brief, ending even prior to forskolin removal. Neither GRH nor SRIH were stimulated by 1,9-dideoxy-forskolin (100 microM), a forskolin analog with cAMP-independent actions. A23187 (5 microM), a calcium ionophore, stimulated the release of SRIH to a much greater extent than that of GRH. The GRH and SRIH secretory responses to PMA (1 microM), a protein kinase C activator, were similar, though delayed. The results suggest that 1) GRH and SRIH secretion are regulated by both protein kinase A and C pathways, and 2) depolarizing agents are important for the release of both hormones.

  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.

  7. Growth hormone-releasing hormone (GHRH polymorphisms associated with carcass traits of meat in Korean cattle

    Directory of Open Access Journals (Sweden)

    Cheong Il-Cheong

    2006-06-01

    Full Text Available Abstract Background Cold carcass weight (CW and longissimus muscle area (EMA are the major quantitative traits in beef cattle. In this study, we found several polymorphisms of growth hormone-releasing hormone (GHRH gene and examined the association of polymorphisms with carcass traits (CW and EMA in Korean native cattle (Hanwoo. Results By direct DNA sequencing in 24 unrelated Korean cattle, we identified 12 single nucleotide polymorphisms within the 9 kb full gene region, including the 1.5 kb promoter region. Among them, six polymorphic sites were selected for genotyping in our beef cattle (n = 428 and five marker haplotypes (frequency > 0.1 were identified. Statistical analysis revealed that -4241A>T showed significant associations with CW and EMA. Conclusion Our findings suggest that polymorphisms in GHRH might be one of the important genetic factors that influence carcass yield in beef cattle. Sequence variation/haplotype information identified in this study would provide valuable information for the production of a commercial line of beef cattle.

  8. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    Science.gov (United States)

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  9. Reproductive characteristics of grass-fed, luteinizing hormone-releasing hormone-immunocastrated Bos indicus bulls.

    Science.gov (United States)

    Hernandez, J A; Zanella, E L; Bogden, R; de Avila, D M; Gaskins, C T; Reeves, J J

    2005-12-01

    Two field trials were conducted in Brazil to evaluate LHRH immunocastration of Bos indicus bulls (d 0 = 2 yr of age). In Study I, 72 bulls were assigned randomly to one of three treatment groups: LHRH0-immunized, castrated, and intact. Immunized animals (n = 25) received a primary and two booster injections of ovalbumin-LHRH-7 and thioredoxin-LHRH-7 fusion proteins on d 0, 141, and 287. Twenty-three bulls were surgically castrated on d 141, and 24 served as intact controls. All animals were slaughtered on d 385, at approximately 3 yr of age. In Study II, 216 bulls were assigned randomly to the same three treatments as in Study I; however, because of a drought in the area, bulls were kept on pasture an additional year, and a fourth treatment was added, in which one-half the LHRH-immunized bulls received an additional booster on d 639 (fourth immunization). All animals in Study II were slaughtered on d 741 (4 yr of age). Luteinizing hormone-releasing hormone antibodies increased following each immunization for immunized bulls, but they were not detectable in castrate or intact animals in either study. Consequently, scrotal circumference was suppressed in immunized bulls compared with intact controls in both studies. By d 287, serum concentrations of testosterone in LHRH-immunized bulls were decreased compared with intact controls (P bulls (173 +/- 22 and 26 +/- 2 g, respectively) and fourth immunization bulls (78 +/- 23 and 20 +/- 2 g, respectively; Study II). At the end of each study, BW was greater (P bulls than for castrated and LHRH-immunized animals. In these two studies, the efficacy of the LHRH fusion proteins to induce an effect similar to that of surgical castration was considered 92 and 93%, respectively. These data support the concept that immunocastration of bulls at 2 yr of age was successful and that it has practical application as a tool for producing grass-fattened bulls in Brazil.

  10. 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.

  11. Response of luteinizing hormone and follicle stimulating hormone to luteinizing hormone-releasing hormone in prepubertal and pubertal chidren, as measured by a highly sensitive immunradiometric assay

    OpenAIRE

    樋口,譲二

    1992-01-01

    To investigate the age-related changes in the pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), the consentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and after LH-RH administra-tion using the highly sensitive immunoradiometric assay (IRMA) in 283 normal children (161 males and 77 females) between 4 and 14 years old and in 22 patients (18 males and 4 females) with pituitary dwarfism. Then, the area of response ...

  12. Expression and purification of growth hormone-releasing factor with the aid of dihydrofolate reductase handle.

    Science.gov (United States)

    Iwakura, M; Obara, K; Kokubu, T; Ohashi, S; Izutsu, H

    1992-07-01

    Expression of a fusion protein composed of dihydrofolate reductase and a derivative of growth hormone-releasing factor resulted in the formation of inclusion bodies in Escherichia coli at 37 degrees C. Among various chemicals, such as detergents, protein denaturants, and acetic acid, tested for the ability to dissolve the inclusion bodies, acetic acid, Brij-35, deoxycholic acid sodium salts, guanidine-HCl, and urea showed a strong solubilizing effect without damaging the DHFR activity. Acetic acid was useful in terms of preparing GRF derivatives, since it could be easily removed by lyophilization, and this made it easy to perform the succeeding BrCN treatment for cutting out the GRF derivative from the fusion protein. The GRF derivative was purified by reversed phase HPLC from the BrCN digest of the acetic acid extract, and its growth hormone-releasing activity was demonstrated. However, for obtaining a highly purified fusion protein itself, solubilization of inclusion bodies by urea was preferred because urea was the only agent which did not cause serious precipitation of the regenerated fusion protein after 10-fold dilution of the extracted inclusion bodies with buffer. The fusion protein was highly purified by means of a methotrexate affinity chromatography.

  13. Specific involvement of gonadal hormones in the functional maturation of growth hormone releasing hormone (GHRH) neurons.

    Science.gov (United States)

    Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G

    2010-12-01

    Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

  14. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma.

    OpenAIRE

    Frohman, L A; Downs, T. R.; Heimer, E P; Felix, A M

    1989-01-01

    The plasma enzyme responsible for primary proteolytic cleavage of growth hormone-releasing hormone (GRH) at the 2-3 amino acid bond was characterized. Native GRH[GRH(1-44)-NH2 and GRH(1-40)-OH], and COOH-terminally shortened fragments [GRH(1-32)-NH2 and GRH(1-29)-NH2] were rapidly cleaved, while GRH(2-32)-NH2 was not degraded at this site. Moreover, degradation to GRH(3-44)-NH2 was unaffected by an aminopeptidase inhibitor, indicating that this metabolite was generated from a single step clea...

  15. Central stimulation of hormone release and the proliferative response of lymphocytes in humans.

    Science.gov (United States)

    Juránková, E; Jezová, D; Vigas, M

    1995-01-01

    The central nervous system (CNS) may communicate with the immune system by direct innervation of lymphoid organs and/or by neurotransmitters and changes in neuroendocrine functioning and hormone release. The consequences of selective transient changes in circulating hormones on immune functioning in humans have not yet been studied. To address this problem, the authors evaluated the lymphoproliferative responses to optimal and suboptimal concentrations of phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement of circulating growth hormone, prolactin, or norepinephrine. The authors failed to demonstrate any effect of elevated growth hormone levels after clonidine challenge on the lymphoproliferative response to mitogens. Similarly, the results did not show any effect of elevated prolactin concentrations induced by domperidone administration on the immune test. Exposure of volunteers to cold resulted in elevation of plasma norepinephrine levels without changes in growth hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of plasma norepinephrine and reduction of the lymphoproliferative response to the suboptimal dosage of PHA. The reduction was significant 180 and 240 min after exposure. These results are indicative of a relationship between norepinephrine and immunity.

  16. Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1987-03-01

    A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical.

  17. Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats.

    Science.gov (United States)

    Pañeda, Covadonga; Arroba, Ana I; Frago, Laura M; Holm, Anne Mette; Rømer, John; Argente, Jesús; Chowen, Julie A

    2003-08-26

    Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

  18. Neither bovine somatotropin nor growth hormone-releasing factor alters expression of thyroid hormone receptors in liver and mammary tissues.

    Science.gov (United States)

    Capuco, A V; Binelli, M; Tucker, H A

    2011-10-01

    Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine to specific nuclear receptors. Organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, have been hypothesized to target the action of thyroid hormones on the mammary gland and play a role in mediating or augmenting a galactopoietic response to bovine somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may be altered by changes in the number or affinity of nuclear receptors for thyroid hormones. In the present study, effects of bST and bovine growth hormone-releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland were studied. Lactating Holstein cows received continuous infusions of bST or bGRF for 63 d or served as uninfused controls. Nuclei were isolated from harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine. Treatments did not alter the capacity or affinity of specific binding sites for triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or retinoid receptor (which may influence thyroid receptor action) expressed in the mammary gland were not altered by bST or bGRF treatment. Data do not support the hypothesis that administration of bST or bGRF alters sensitivity of mammary tissue by changing expression of thyroid hormone receptors.

  19. Myogenic expression of an injectable protease-resistant growth hormone-releasing hormone augments long-term growth in pigs

    Science.gov (United States)

    Draghia-Akli, R.; Fiorotto, M. L.; Hill, L. A.; Malone, P. B.; Deaver, D. R.; Schwartz, R. J.

    1999-01-01

    Ectopic expression of a new serum protease-resistant porcine growth hormone-releasing hormone, directed by an injectable muscle-specific synthetic promoter plasmid vector (pSP-HV-GHRH), elicits growth in pigs. A single 10 mg intramuscular injection of pSP-HV-GHRH DNA followed by electroporation in three-week-old piglets elevated serum GHRH levels by twofold to fourfold, enhanced growth hormone secretion, and increased serum insulin-like growth factor-I by threefold to sixfold over control pigs. After 65 days the average body weight of the pigs injected with pSP-HV-GHRH was approximately 37% greater than the placebo-injected controls and resulted in a significant reduction in serum urea concentration, indicating a decrease in amino acid catabolism. Evaluation of body composition indicated a uniform increase in mass, with no organomegaly or associated pathology.

  20. Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release.

    Science.gov (United States)

    Sirotkin, Alexander V; Harrath, Abdel Halim; Grossmann, Roland

    2016-11-01

    The aim of the present experiments was to examine the species-specific and cell-specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells.

  1. Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

    Institute of Scientific and Technical Information of China (English)

    Wen-Cai Qiu; Zhi-Gang Wang; Wei-Gang Wang; Jun Yan; Qi Zheng

    2008-01-01

    AIM:To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6(GHRP-6) in diabetic mice with gastric motility disorders.METHODS:A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan.Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg),and the effects on gastric emptying were measured after intragastric application of phenol red.The effect of atropine,NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg)was also investigated.The effects of ghrelin or GHRP-6(0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro,in gastric fundic circular strips taken from diabetic mice.The presence of growth hormone secretagogue receptor la transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR).RESULTS:We established a diabetic mouse model with delayed gastric emptying.Ghrelin and GHRP-6accelerated gastric emptying in diabetic mice with gastroparesis.In the presence of atropine or L-NAME,which delayed gastric emptying,ghrelin and GHRP-6(100 μg/kg) failed to accelerate gastric emptying.D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist.Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic mice.RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.CONCLUSION:Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis,perhaps by activating peripheral cholinergic pathways in the enteric nervous system.

  2. Structural study of human growth hormone-releasing factor fragment (1?29) by vibrational spectroscopy

    Science.gov (United States)

    Carmona, P.; Molina, M.; Lasagabaster, A.

    1995-05-01

    The conformational structure of fragment 1-29 of human growth hormone releasing factor, hGHRF (1-29), in aqueous solution and in the solid state is investigated by infrared and Raman spectroscopy. The polypeptide backbone is found to be unordered in the solid state. However, the spectra of the peptide prepared as 5% (w/w) aqueous solutions show that approximately 28% of the peptide is involved in intermolecular β-sheet aggregation. The remainder of the peptide exists largely as disordered and β-sheet conformations with a small portion of α-helices. Tyrosine residues are found to be exposed to the solvent. The secondary structures are quantitatively examined through infrared spectroscopy, the conformational percentages being near those obtained by HONDAet al. [ Biopolymers31, 869 (1991)] using circular dichroism. The fast hydrogen/deuterium exchange in peptide groups and the absence of any NMR sign indicative of ordered structure [ G. M. CLOREet al., J. Molec. Biol.191, 553 (1986)] support that the solution conformations of the non-aggregated peptide interconvert in dynamic equilibrium. Some physiological advantages that may derive from this conformational flexibility are also discussed

  3. L-arginine promotes gut hormone release and reduces food intake in rodents.

    Science.gov (United States)

    Alamshah, A; McGavigan, A K; Spreckley, E; Kinsey-Jones, J S; Amin, A; Tough, I R; O'Hara, H C; Moolla, A; Banks, K; France, R; Hyberg, G; Norton, M; Cheong, W; Lehmann, A; Bloom, S R; Cox, H M; Murphy, K G

    2016-05-01

    To investigate the anorectic effect of L-arginine (L-Arg) in rodents. We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  4. L‐arginine promotes gut hormone release and reduces food intake in rodents

    Science.gov (United States)

    Alamshah, A.; McGavigan, A. K.; Spreckley, E.; Kinsey‐Jones, J. S.; Amin, A.; Tough, I. R.; O'Hara, H. C.; Moolla, A.; Banks, K.; France, R.; Hyberg, G.; Norton, M.; Cheong, W.; Lehmann, A.; Bloom, S. R.; Cox, H. M.

    2016-01-01

    Aims To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents. Methods We investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. Results Oral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats. Conclusions L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity. PMID:26863991

  5. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    Science.gov (United States)

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  6. 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.

  7. Decreased hypothalamic growth hormone-releasing hormone content and pituitary responsiveness in hypothyroidism.

    OpenAIRE

    Katakami, H; Downs, T. R.; Frohman, L A

    1986-01-01

    The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and...

  8. Conformational origin of a difficult coupling in a human growth hormone releasing factor analog.

    Science.gov (United States)

    Deber, C M; Lutek, M K; Heimer, E P; Felix, A M

    1989-01-01

    During the solid-phase synthesis of the human growth hormone releasing factor (GRF) analog [Ala15, Leu27, Asn28] -GRF(1-32)-OH, incorporation of Boc-Gln16 was determined to be incomplete. While aggregation of growing resin-bound peptide chains with concomitant beta-sheet formation and "precipitation" has been proposed to account in general for such "difficult coupling," no feature of sequence in the Gln16 region of this GRF analog provided an immediate rationale for this result. We now report 500 MHz 1H NMR spectra of a series of resin-bound GRF segments surrounding the Gln16 position (19-32 through 14-32), swelled in dimethylsulfoxide-d6 solutions [GRF(14-32) = Leu14-Ala-Gln-Leu-Ser(Bzl)-Ala-Arg(Tos)-Lys(CIZ)-Leu- Leu-Gln-Asp(OcHex)-Ile-Leu-Asn-Arg(Tos)-Gln-Gln-Gly32-PAM resin]. While relatively sharp spectra are observed for GRF(19-32), components with resonances broadened by an order-of-magnitude appear in spectra of the 18-32 and 17-32 peptide-resin, and the entire spectrum of 16-32 is ill-resolved and highly broadened. Subsequent spectra sharpen again (15-32, 14-32). These combined synthesis/spectroscopic experimental results, in conjunction with predictive analyses using standard Chou-Fasman 2 degrees structure parameters, suggest that the completeness of the Gln16 coupling is hindered by formation of a specific, folded beta-sheet/beta-turn structure in GRF(16-32) (with the turn located at 18-21, "upstream" of the difficult coupling site), and accompanying aggregation of peptide chains. This analysis suggests that awareness of such potential beta-sheet/beta-turn sequences can guide analog choices, and/or facilitate pre-programming of synthesis steps in anticipation of problem couplings.

  9. Identification of the growth-hormone-releasing peptide-2 (GHRP-2) in a nutritional supplement.

    Science.gov (United States)

    Thomas, Andreas; Kohler, Maxie; Mester, Joachim; Geyer, Hans; Schänzer, Wilhelm; Petrou, Michael; Thevis, Mario

    2010-03-01

    Black market products of a pharmaceutical nature and nutritional supplements have received substantial and increasing attention because of potential performance enhancement in elite and non-professional sports. In addition, improved general health is claimed for non-competing individuals. The risks and foreseeable dangers of the uncontrolled use of highly potent and non-approved pharmaceutical compounds in healthy individuals are of considerable concern. In the present case report, the emerging drug candidate GHRP-2 with verified growth-hormone-releasing properties was identified and quantified in tablets offered as an over-the-counter nutritional supplement. The impact of this orally active peptide on the hGH/IGF-axis has been established for several years and its illicit use in elite sports has been assumed. As a releasing factor for hGH, GHRP-2 belongs to the list of substances prohibited by the World Anti-Doping Agency (WADA). Unfortunately, to date there is no routinely performed assay for the determination of these peptides potentially occurring in biological fluids of competing athletes, but the present data will facilitate the implementation by providing principle analytical information on liquid chromatographic and mass spectrometric behaviour. Qualitative identification of the target analyte after extraction from the tablet matrix was performed by high resolution/high accuracy mass spectrometry after liquid chromatographic separation under consideration of the accurate masses and the ratios of the protonated molecules and their fragment ions derived from their collisionally induced dissociation. Quantitative results were obtained by means of liquid chromatography coupled to a triple quadrupole mass spectrometer and linear regression using an external calibration curve (with GHRP-2 reference compound) adjusted via internal standard (Hexarelin). Hereby, the content of GHRP-2 was determined with approximately 50 µg per tablet.

  10. 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 pituita...... somatotrophs or mammosomatotrophs to cells with features of the glycoprotein hormone cell line. These findings provide conclusive evidence that protracted GRH stimulation of secretory activity can result in proliferation, hyperplasia, and adenoma of adenohypophysial cells....

  11. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    Science.gov (United States)

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

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

    OpenAIRE

    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 w...

  13. 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.

  14. Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

    Directory of Open Access Journals (Sweden)

    Daniele Leão Ignacio

    Full Text Available 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.

  15. 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; Carvalho, Denise P; Werneck-de-Castro, João Pedro

    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.

  16. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro

    NARCIS (Netherlands)

    L.J. Hofland (Leo); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven); A. Beckers (Albert); J. van der Hoek (Joost); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); M. Waaijers (Marlijn); D. Sprij-Mooij (Diana); C. Bruns (Christian); G. Weckbecker (Gisbert); R.A. Feelders (Richard)

    2004-01-01

    textabstractTo determine the inhibitory profile of the novel somatostatin (SRIF) analog SOM230 with broad SRIF receptor binding, we compared the in vitro effects of SOM230, octreotide (OCT), and SRIF-14 on hormone release by cultures of different types of secreting pituitary adenom

  17. Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Folkers, K.; Bowers, C.Y.; Tang, P.L.; Kubota, M.

    1986-02-01

    Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known agonist analogs of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. The authors have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and they found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: (HisV,TrpX,GlnY)LHRH; (HisV,TrpX,LeuY)LHRH; (HisV,TrpX)LHRH; (TrpX)LHRH; (HisV)LHRH. These structures are a basis for the design of antagonists without ArgY toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of ArgY and GlnY or LeuY antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. Radioreceptor assays and radioimmunoassays were utilized.

  18. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, (D-Mel{sup 6})LH-RH (SB-05) and (Ac-D-Nal(2){sup 1},D-Phe(pCl){sup 2},D-Pal(3){sup 3},Arg{sup 5},D-Mel{sup 6},D-Ala{sup 10})LH-RH (SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine) possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel{sup 6} analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

  19. 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.

  20. Facilitation of lordosis in rats by a metabolite of luteinizing hormone releasing hormone.

    Science.gov (United States)

    Wu, T J; Glucksman, Marc J; Roberts, James L; Mani, Shaila K

    2006-05-01

    In the female rat, ovulation is preceded by a marked increase in the release of the decapeptide, LHRH, culminating in a preovulatory LH surge, which coincides with a period of sexual receptivity. The decapeptide, LHRH, is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its metabolite, LHRH-(1-5). Given the central function of LHRH in reproduction and reproductive behavior, we examined the role of the metabolite, LHRH-(1-5), in mediation of LHRH-facilitated reproductive behavior. Intracerebroventricular administration of LHRH-(1-5) facilitated sexual behavior responses, similar to those facilitated by the decapeptide LHRH, in ovariectomized estradiol-primed female rats. Furthermore, immunoneutralization of EP24.15 resulted in the inhibition of the LHRH-facilitated lordosis but had no inhibitory effects on LHRH-(1-5)-facilitated lordosis. The LHRH antagonist, Antide, was capable of inhibiting LHRH-facilitated lordosis, without affecting LHRH-(1-5)-facilitated lordosis. Collectively, these results suggest a role for LHRH metabolites in the facilitation of female receptive behavior in rats.

  1. Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans

    Directory of Open Access Journals (Sweden)

    Joanne L. Calley

    2014-01-01

    Full Text Available The kisspeptins are a family of neuropeptides which act as upstream stimulators of gonadotrophin releasing hormone (GnRH neurons. Kisspeptin signalling is prerequisite to establishing the normal human reproductive phenotype; loss of function mutations in the KISS1 or KISS1R gene produces normosmic hypogonadotrophic hypogonadism in humans and mice, whilst increased activation of KISS1R causes precocious puberty. Administration of exogenous kisspeptin to human subjects stimulates an acute gonadotrophin rise. Serum kisspeptin levels also markedly increase during pregnancy. The identification of kisspeptin has been one of the biggest discoveries in the field of reproductive endocrinology, since the isolation and sequencing of GnRH in 1977, and has generated a novel research avenue which has received much attention over the past decade. This research has delineated many properties of the KISS1-KISS1R system, but there is still further work to do. Understanding kisspeptin’s role throughout our reproductive lifetime should help us better understand—and therefore treat—disorders of reproductive function. Promisingly, the current data supports the potential to develop kisspeptin based therapies. As an outlook article this paper focusses predominantly on our groups recent investigations into the effects of kisspeptin administration to humans and the potential therapeutic role of kisspeptin.

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

    Science.gov (United States)

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

    2013-11-01

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

  3. The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release.

    Science.gov (United States)

    Kola, Blerina; Wittman, Gábor; Bodnár, Ibolya; Amin, Faisal; Lim, Chung Thong; Oláh, Márk; Christ-Crain, Mirjam; Lolli, Francesca; van Thuijl, Hinke; Leontiou, Chrysanthia A; Füzesi, Tamás; Dalino, Paolo; Isidori, Andrea M; Harvey-White, Judith; Kunos, George; Nagy, György M; Grossman, Ashley B; Fekete, Csaba; Korbonits, Márta

    2013-12-01

    This study aimed to investigate whether the growth hormone release and metabolic effects of ghrelin on AMPK activity of peripheral tissues are mediated by cannabinoid receptor type 1 (CB1) and the central nervous system. CB1-knockout (KO) and/or wild-type mice were injected peripherally or intracerebroventricularly with ghrelin and CB1 antagonist rimonabant to study tissue AMPK activity and gene expression (transcription factors SREBP1c, transmembrane protein FAS, enzyme PEPCK, and protein HSL). Growth hormone levels were studied both in vivo and in vitro. Peripherally administered ghrelin in liver, heart, and adipose tissue AMPK activity cannot be observed in CB1-KO or CB1 antagonist-treated mice. Intracerebroventricular ghrelin treatment can influence peripheral AMPK activity. This effect is abolished in CB1-KO mice and by intracerebroventricular rimonabant treatment, suggesting that central CB1 receptors also participate in the signaling pathway that mediates the effects of ghrelin on peripheral tissues. Interestingly, in vivo or in vitro growth hormone release is intact in response to ghrelin in CB1-KO animals. Our data suggest that the metabolic effects of ghrelin on AMPK in peripheral tissues are abolished by the lack of functional CB1 receptor via direct peripheral effect and partially through the central nervous system, thus supporting the existence of a possible ghrelin-cannabinoid-CB1-AMPK pathway.

  4. 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

  5. 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.

  6. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  7. Effect of permeation enhancer pretreatment on the iontophoresis of luteinizing hormone releasing hormone (LHRH) through human epidermal membrane (HEM).

    Science.gov (United States)

    Smyth, Hugh D C; Becket, Gordon; Mehta, Samir

    2002-05-01

    A 2 x 2 factorial design was performed to determine the effect of a permeation enhancer (oleic acid/propylene glycol), iontophoresis (2 V), and the combination of the two treatments on the permeation enhancement of a model peptide, LHRH (luteinizing hormone releasing hormone), through human epidermal membrane (HEM). In parallel studies, TEAB (tetraethylammonium bromide, a small ionic solute) and sucrose (an electroosmotic flow marker) were also investigated. Structural changes in the HEM were monitored via conductance measurements, differential scanning calorimetry (DSC), and infrared (IR) spectroscopy experiments. LHRH enhancement due to enhancer in combination with iontophoresis (I + E; 29.5 times passive permeability, P), was greater than during iontophoresis alone (I; 14.3) and enhancer treatment alone (E; 3.5). I + E had an additive effect of I and E, indicating the mechanisms of action of the individual enhancement strategies were likely to be located at different sites in the skin. Also, no synergistic enhancement was observed with I + E for either TEAB or sucrose. For TEAB, permeability enhancement due to I (approximately 1400) was much higher than that due to E (14.9), and no additive effect could be detected. For sucrose, E had no effect on either passive or iontophoretic permeability, eliminating the possibility that electroosmosis could explain increases in LHRH permeability. Evidence of synergy between E and I was found, with conductance measurements indicating that I + E synergistically increased the membrane permeability to conducting ions (Na+ and Cl-). It appears these pathways were not available for transport for the solutes used in the current study. DSC and IR investigations showed significant changes in stratum corneum lipid structure following E treatment but not following I. These findings probably arise from the localized action of iontophoresis compared with the bulk action of enhancer. In summary, increased LHRH delivery through HEM in

  8. Discordant effects of endogenous and exogenous somatostatin on growth hormone-releasing hormone secretion from perifused mouse hypothalami.

    Science.gov (United States)

    Pecori Giraldi, F; Frohman, L A

    1995-05-01

    The role of somatostatin (SRIF) on growth hormone-releasing hormone (GRH) secretion has been controversial because of discordant findings that may be model dependent. We have examined possible explanations for these findings by altering endogenous and exogenous SRIF tone in a mouse hypothalamic perifusion system. Four mediobasal hypothalamic fragments were perifused in a single chamber for 6 h. After a 2-hour equilibration period, test substances were introduced and maintained throughout the perifusion. After an additional 2 h, fragments were submaximally stimulated with 30 mM K+. Depletion of tissue SRIF by 10(-3) M cysteamine increased K(+)-stimulated GRH release 2-fold without altering basal GRH secretion. Removal of endogenous SRIF tone by anti-SRIF serum also augmented the GRH response to K+. Perifusion of SRIF at concentrations ranging from 10(-12) to 10(-8) M significantly increased the GRH response to K+ in a dose-dependent manner. A significant increase was also observed during the perifusion of 10(-9) M octreotide. Simultaneous perifusion with anti-SRIF serum and 10(-9) M octreotide (to which the antibody does not bind) resulted in a response of GRH to K+ that was similar to that observed with anti-SRIF serum alone. Combined perifusion with cysteamine and 10(-9) M SRIF also resulted in a GRH response to K+ that did not differ from the response observed during cysteamine alone. The enhancement of GRH secretion by reduction of endogenous SRIF tone or tissue content implies an inhibitory role of endogenous SRIF on GRH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Identification of the growth hormone-releasing hormone analogue [Pro1, Val14]-hGHRH with an incomplete C-term amidation in a confiscated product.

    Science.gov (United States)

    Esposito, Simone; Deventer, Koen; Van Eenoo, Peter

    2014-01-01

    In this work, a modified version of the 44 amino acid human growth hormone-releasing hormone (hGHRH(1-44)) containing an N-terminal proline extension, a valine residue in position 14, and a C-terminus amidation (sequence: PYADAIFTNSYRKVVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 ) has been identified in a confiscated product by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Investigation of the product suggests also an incomplete C-term amidation. Similarly to other hGHRH analogues, available in black markets, this peptide can potentially be used as performance-enhancing drug due to its growth hormone releasing activity and therefore it should be considered as a prohibited substance in sport. Additionally, the presence of partially amidated molecule reveals the poor pharmaceutical quality of the preparation, an aspect which represents a big concern for public health as well.

  10. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Istvan eCzikora

    2014-07-01

    Full Text Available Rationale. Antibiotic treatment of patients infected with G- or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS and pneumolysin (PLY in their lungs. Growth Hormone-releasing Hormone (GHRH agonist JI-34 protects human lung microvascular cells (HL-MVEC, expressing splice variant 1 (SV-1 of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated PKA depletion.Methods. Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye incorporation. Cytokine generation in broncho-alveolar lavage fluid was measured by multiplex analysis. PKA and PKC-alpha activity were assessed by Western blotting. Results. GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-alpha activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions. GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-alpha-induced pathway in the presence of PLY, the former of which dominates the latter.

  11. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    Science.gov (United States)

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

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

    OpenAIRE

    Rimmele, U; Spillmann, M; Bärtschi, C; Wolf, O.T.; Weber, C S; Ehlert, Ulrike; Wirtz, P H

    2009-01-01

    RATIONALE: Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. OBJECTIVES: 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. MATERIALS AND METHODS: Fifty healthy young men received a single oral dose of either 3...

  13. 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…

  14. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.

    OpenAIRE

    Frohman, L A; Downs, T. R.; Williams, T C; Heimer, E P; Pan, Y C; Felix, A M

    1986-01-01

    The effect of plasma on degradation of human growth hormone-releasing hormone (GRH) was examined in vitro and in vivo using high performance liquid chromatography (HPLC), radioimmunoassay (RIA), and bioassay. When GRH(1-44)-NH2 was incubated with human plasma, the t1/2 of total GRH immunoreactivity was 63 min (RIA). However, HPLC revealed a more rapid disappearance (t1/2, 17 min) of GRH(1-44)-NH2 that was associated with the appearance of a less hydrophobic but relatively stable peptide that ...

  15. Possible participation of calcium in growth hormone release and in thyrotropin-releasing hormone and human pancreatic growth hormone-releasing factor synergy in a primary culture of chicken pituitary cells.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-09-01

    We previously reported that thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) exert synergistic (greater than additive) effects on growth hormone (GH) release from chicken pituitary cells in primary culture. In the present studies the possible participation of calcium in GH release and in TRH and hpGRF synergy was investigated. Following dispersion with collagenase, cells were cultured for 48 hr prior to exposure (2 hr) to test agents. Cultured cells were exposed to a range of calcium concentrations (0, 0.02, 0.2, and 2.0 mM) in the presence and absence of secretagogues. These results demonstrated that basal GH release was not altered by the concentration of calcium in the medium: however, secretagogue-induced GH release required calcium. Thus, TRH, hpGRF, 8 Br-cAMP, or forskolin stimulated GH release in the absence of calcium. Furthermore, synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, or forskolin was observed only at the highest calcium concentration (2.0 mM). In other studies, ionomycin (10(-5) M), a calcium ionophore, stimulated GH release to a value about 125% over the basal (absence of test agent) value. Ionomycin-induced GH release was not affected by TRH (5.0 ng/ml); the combined effects of ionomycin (10(-7)-10(-5) M) and hpGRF (5.0 ng/ml) on GH release were less than additive. However, ionomycin (10(-5) M) further increased GH release over that resulting from the synergistic action of TRH and hpGRF (5.0 ng/ml each). Verapamil (a calcium channel blocker) did not affect GH release induced by either TRH or hpGRF (5.0 ng/ml each). However, this agent did inhibit synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, forskolin, or isobutylmethylxanthine. These results suggest that calcium participates in secretagogue-induced GH release from chicken somatotrophs in vitro.

  16. Blockade of LH release and ovulation in the rabbit with inhibitory analogues of luteinizing hormone releasing hormone.

    Science.gov (United States)

    Phelps, C P; Coy, D H; Schally, A V; Sawyer, C H

    1977-06-01

    Plasma LH levels and ovulation were studied in female rabbits following administration of several inhibitory analogues of luteinizing hormone-releasing hormone (LHRH) before and after mating with experienced males. Administration of (D-Phe2, D-Leu6)-LHRH (1.5 mg/kg sc) to does 30 min before mating did not prevent either LH release or ovulation. However, a single sc injection of (D-Phe2, L-Phe3, D-Phe6y-LHRH (6 mg/kg) given 30 min before mating in 4 rabbits resulted in a 30-60 min delay in the coitus-induced release of LH when compared with post-coital changes in the same animals injected with vehicle; however, all of the does ovulated. When multiple dosages of 4 mg/kg (D-Phe2, L-Phe3, D-Phe6)-LHRH were administered 3-5 times at half-hourly intervals beginning 30 min prior to mating there was a considerable reduction in plasma LH elevations at 0.5, 1.0, 2.0 and 4.0 h after mating and 3/5 treated rabbits showed partial or complete blockade of ovulation. Quite similar results were obtained with the same dosage of (D-Phe2, D-Trp3, D-Phe6)-LHRH. An early sharp peak in LH release and full ovulation were stimulated in 6 out of 6 does by a single iv injection of synthetic LHRH (500 ng/kg). However, in another experiment, three half-hourly sc injections (4 mg/kg) of (D-Phe2, L-Phe3, D-Phe6)-LHRH beginning 30 min before administering LHRH markedly reduced the rise in plasma LH (P less than 0.01) and completely blocked ovulation in all of the same 6 animals. An unsuccessful attempt was made to provide a test animal for LHRH analogue investigations by implanting 4 cm of silastic tubing filled with crystalline estradiol (E2) sc in ovariectomized (OVX) AND INTACT DOES. In OVX does the silastic E2 implants resulted in a progressive decline in the ability to release LH in response to mating at 6 and at 20 days after implantation. With ovaries present, the E2 implant permitted post-coital LH release and ovulation at 4 d but not at 30 d post-implantation. At 30 d after removal of

  17. Postural changes associated with public speech tests lead to mild and selective activation of stress hormone release.

    Science.gov (United States)

    Mlynarik, M; Makatsori, A; Dicko, I; Hinghofer-Szalkay, H G; Jezova, D

    2007-03-01

    We tested whether simulation of postural changes, which occur during public speech test procedures, activates cardiovascular system and stress hormone release that could interfere with the effect of psychosocial stress load. Young healthy male volunteers (n=8) underwent procedure imitating exactly all postural changes present in the psychosocial stress model based on public speech used in this laboratory (namely changes from sitting to standing and repeated sitting). Postural changes were associated with increases in heart rate, blood pressure, plasma concentrations of noradrenaline and aldosterone and elevation in plasma renin activity. In contrast to cardiovascular parameters, adrenocorticotropic hormone, cortisol and adrenaline, the main characteristics of hormonal response during mental stress, were not significantly influenced. The overall magnitude of all observed alterations was much smaller than that seen following mental stress procedures in our previous studies. This study provides evidence that changes in body posture during public speech test procedure influence hemodynamics and endocrine responses in a mild manner. Though this influence may represent a source of unspecific variance, substantial confounding effects on responses to the psychosocial component of the procedure are unlikely. In any case, models combining mental stressors and changes in body posture must be interpreted as complex stress stimuli.

  18. 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.

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

    Science.gov (United States)

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karin; Harrath, Abdel Halim; Kotwica, Jan

    2016-01-21

    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.

  20. Dissociation between the effects of somatostatin (SS) and octapeptide SS-analogs on hormone release in a small subgroup of pituitary- and islet cell tumors

    NARCIS (Netherlands)

    L.J. Hofland (Leo); W.W. de Herder (Wouter); H.A. Visser-Wisselaar (Heleen); C. van Uffelen; M. Waaijers (Marlijn); J. Zuyderwijk; P. Uitterlinden (Piet); P.M. van Koetsveld (Peter); S.W.J. Lamberts (Steven); J.M. Kros (Johan)

    1997-01-01

    textabstractThe effects of somatostatin (SS-14 and/or SS-28) and of the three octapeptide SS-analogs that are available for clinical use (octreotide, BIM-23014 and RC-160) on hormone release by primary cultures of 15 clinically nonfunctioning pituitary adenomas (NFA), 7

  1. Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.

    Science.gov (United States)

    Noel, G L; Dimond, R C; Earll, J M; Frantz, A G

    1976-05-01

    Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.

  2. 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 oral...... improved. The natural peptide is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV), but resistant analogs as well as inhibitors of DPP IV are now under development, and both approaches have shown remarkable efficacy in experimental and clinical studies....

  3. 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.

  4. Alpha-adrenergic regulation of growth hormone release after electroconvulsive therapy in man.

    Science.gov (United States)

    Vigas, M; Wiedermann, V; Németh, S; Jurcovicová, J; Zigo, L

    1976-01-01

    When electroshcok therapy was administered to male psychiatric patients without anticonvulsive premedication, serum growth hormone (GH) increased; the increase was not prevented by an infusion of 20% glucose (5 ml per min) 20 min prior to electroshock. Therefore, the GH rise is not caused by muscle exercise during convulsions. Infusing 30 mg of phentolamine 40 min prior to electroshcok inhibited the GH response. Phentolamine's effect shows that the stress-induced GH release that follows electroconvulsive therapy is mediated by alpha-adrenergic neurons.

  5. 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.

  6. 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.

  7. 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.

  8. Diacylglycerol acyltransferase-1 (DGAT1 inhibition perturbs postprandial gut hormone release.

    Directory of Open Access Journals (Sweden)

    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.

  9. Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells.

    Science.gov (United States)

    Phelps, C J; Wiggins, J P; Wangsness, P J

    1988-10-01

    A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.

  10. 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 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 < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

  11. Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats.

    Science.gov (United States)

    Iwata, Kinuyo; Kunimura, Yuyu; Matsumoto, Keisuke; Ozawa, Hitoshi

    2017-06-01

    Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities. © 2017 Society for Endocrinology.

  12. QSAR models for predicting the activity of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A using quantum chemical properties.

    Science.gov (United States)

    Fernández, Michael; Caballero, Julio

    2007-04-01

    Multiple linear regression (MLR) combined with genetic algorithm (GA) and Bayesian-regularized Genetic Neural Networks (BRGNNs) were used to model the binding affinity (pK(I)) of 38 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A for the Human Luteinizing Hormone-Releasing Hormone (LHRH) receptor using quantum chemical descriptors. A multiparametric MLR equation with good statistical quality was obtained that describes the features relevant for antagonistic activity when the substituent at the position 3 of the erythronolide core was varied. In addition, four-descriptor linear and nonlinear models were established for the whole dataset. Such models showed high statistical quality. However, the BRGNN model was better than the linear model according to the external validation process. In general, our linear and nonlinear models reveal that the binding affinity of the compounds studied for the LHRH receptor is modulated by electron-related terms.

  13. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice

    Institute of Scientific and Technical Information of China (English)

    Simona Perboni; Cyril Bowers; Shinya Kojima; Akihiro Asakawa; Akio Inui

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo-therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin ago-nist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU + GHRP-2 significantly increased com-pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P = 0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  14. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

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    Yi-Ning Chao

    2016-08-01

    Full Text Available Cyclooxygenase-2 (COX-2 and interleukin-8 (IL-8 are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC activator phorbol 12, 13-didecanoate (PDD and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2. GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2 and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1 reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1 and protein phosphatase 2 (PP2A reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2 in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A.

  15. Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

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    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.

  16. 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.

  17. Effects of ionizing radiation and pretreatment with (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O' Connell, G.; Belbeck, L.

    1987-10-01

    To assess the effects of a gonadotropin-releasing hormone agonist, (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

  18. Central administration of growth hormone-releasing hormone triggers downstream movement and schooling behavior of chum salmon (Oncorhynchus keta) fry in an artificial stream.

    Science.gov (United States)

    Ojima, Daisuke; Iwata, Munehico

    2009-03-01

    Anadromous salmonids migrate downstream to the ocean (downstream migration). The neuroendocrine mechanism of triggering the onset of downstream migration is not well known. We investigated the effects of 14 chemicals, including neuropeptides, pineal hormones, neurotransmitters, and neuromodulators (growth hormone-releasing hormone: GHRH, thyrotropin-releasing hormone, corticotropin-releasing hormone: CRH, gonadotropin-releasing hormone, melatonin, N-acetyl serotonin, serotonin, beta-endorphin, enkephalin, dopamine, norepinephrine, epinephrine, acetylcholine, and histamine) on the onset of downstream migration in chum salmon (Oncorhynchus keta) fry. We defined downstream migration as a downstream movement (negative rheotaxis) with schooling behavior and counted the number of downstream movements and school size in experimental circulation tanks. An intracerebroventricular injection of GHRH, CRH, melatonin, N-acetyl serotonin, or serotonin stimulated the number of downstream movements. However, GHRH was the only chemical that also stimulated an increase in schooling behavior. These results suggest that CRH, melatonin, N-acetyl serotonin, and serotonin are involved in the stimulation of downstream movement in chum salmon, while GHRH stimulates both downstream movement and schooling behavior.

  19. 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...

  20. Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.

    Science.gov (United States)

    Kuba, Sayaka; Ishida, Mayumi; Oikawa, Masahiro; Nakamura, Yoshiaki; Yamanouchi, Kosho; Tokunaga, Eriko; Taguchi, Kenichi; Esaki, Taito; Eguchi, Susumu; Ohno, Shinji

    2016-11-01

    The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

  1. Semaphorin Signaling in the Development and Function of the Gonadotropin Hormone-Releasing Hormone (GnRH System

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    Andrea eMessina

    2013-09-01

    Full Text Available The semaphorin proteins are among the best-studied families of guidance cues, contributing to morphogenesis and homeostasis in a wide range of tissue types. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors are capable to mediate signaling by semaphorins. These guidance proteins were originally identified as growth cone collapsing factors or as inhibitory signals, crucial for nervous system development. Since those seminal discoveries, the list of functions of semaphorins has rapidly grown. Over the past few years, a growing body of data indicates that semaphorins are involved in the regulation of the immune and vascular systems, in tumor growth/cancer cell metastasis and in neural circuit formation. Recently there has been increasing emphasis on research to determine the potential influence of semaphorins on the development and homeostasis of hormone systems and how circulating reproductive hormones regulate their expression and functions. Here, we focus on the emerging role of semaphorins in the development, differentiation and plasticity of unique neurons that secrete gonadotropin-releasing hormone (GnRH, which are essential for the acquisition and maintenance of reproductive competence in all vertebrates. Genetic evidence is also provided showing that insufficient semaphorin signaling contributes to some forms of reproductive disorders in humans, characterized by the reduction or failure of sexual competence.Finally, we will review some studies with the goal of highlighting how the expression of semaphorins and their receptors might be regulated by gonadal hormones in physiological and pathological conditions.

  2. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  3. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Directory of Open Access Journals (Sweden)

    Pooria Mansoori

    2011-07-01

    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

  4. Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS.

    Science.gov (United States)

    Knoop, Andre; Thomas, Andreas; Fichant, Eric; Delahaut, Philippe; Schänzer, Wilhelm; Thevis, Mario

    2016-05-01

    The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIA™ D.A.R.T.'S® (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19-37%), lower limit of detection (sports drug testing samples. Further studies are however required and warranted to account for potential species-related differences in metabolism and elimination of the target analytes.

  5. Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies.

    Science.gov (United States)

    Stanley, Takara L; Grinspoon, Steven K

    2015-04-01

    Increased visceral adipose tissue (VAT) is associated with reductions in endogenous GH secretion, possibly as a result of hyperinsulinemia, increased circulating free fatty acid, increased somatostatin tone, and reduced ghrelin. Reduced GH may, in turn, further exacerbate visceral fat accumulation because of decreased hormone-sensitive lipolysis in this depot. Data from multiple populations demonstrate that both reduced GH and increased VAT appear to contribute independently to dyslipidemia, increased systemic inflammation, and increased cardiovascular risk. The reductions in GH in states of visceral adiposity are characterized by reduced basal and pulsatile GH secretion with intact pulse frequency. Treatment with GH-releasing hormone (GHRH) provides a means to reverse these abnormalities, increasing endogenous basal and pulsatile GH secretion without altering pulse frequency. This review describes data from HIV-infected individuals and individuals with general obesity showing that treatment with GHRH significantly reduces visceral fat, ameliorates dyslipidemia, and reduces markers of cardiovascular risk. Further research is needed regarding the long-term efficacy and safety of this treatment modality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Seasonal differences in the parameters of luteinizing hormone release to exogenous gonadotropin releasing hormone in prepubertal Holstein heifers in Sapporo.

    Science.gov (United States)

    Kadokawa, Hiroya

    2007-02-01

    Stress due to summer heat has adverse effects on reproduction in Holstein dairy cattle. Summer suppression of reproduction of Holsteins can pose an important economic problem, even in Hokkaido prefecture located in the northern region of Japan. Hokkaido is one of the most important dairy farming areas of Japan. This study is an attempt to clarify the seasonal differences in the parameters of luteinizing hormone (LH) response to exogenous gonadotropin releasing hormone (GnRH) in Sapporo, Hokkaido, Japan. A total of 12 prepubertal heifers received an injection with GnRH analogue intramuscularly in either May (n=4, May group), July (n=4, July group), or November (n=4, November group), and serial blood samples were collected to analyze the parameters of the LH response curve after GnRH injection. The parameters were as follows: the basal LH concentration, peak LH concentration, duration from the time of GnRH injection to the time of the peak LH concentration, and area under the LH response curve (AUC). There were no significant differences in the basal and peak LH concentrations or the AUC among the three groups. The July group reached the LH peak significantly (P<0.05) faster than the May group, but there was no significant difference with the November group. Therefore, the results of the present study do not demonstrate an effect of summer heat on the LH response to the exogenous GnRH in Holstein heifers.

  7. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    Science.gov (United States)

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (psleep and slow-wave activity was reduced (pgrowth impairment (pgrowth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  8. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    Energy Technology Data Exchange (ETDEWEB)

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

  9. Structure and Function of Growth Hormone Releasing Peptide(Ghrelin)%生长激素释放肽的结构和功能

    Institute of Scientific and Technical Information of China (English)

    应牡英

    2006-01-01

    生长激素释放肽(growth hormone releasing peptide,Ghrelin,GHRP),是最近发现的可以促进GH分泌的肽激素,主要来源于胃,有28个氨基酸残基,其第三位氨基酸残基(一般是丝氨酸)被脂肪酸修饰,实验证明被修饰的N端是其活性核心部位.该文介绍ghrelin的主要结构和生物学功能.

  10. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Schally, A.V.; Paz-Bouza, J.I.; Schlosser, J.V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.

    1987-02-01

    Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist (D-Trp/sup 6/)LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist (D-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

  11. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men.

    Science.gov (United States)

    Deslypere, J P; Kaufman, J M; Vermeulen, T; Vogelaers, D; Vandalem, J L; Vermeulen, A

    1987-01-01

    The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.

  12. 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.

  13. Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry.

    Science.gov (United States)

    Ozawa, Hitoshi; Han, Fang; Kawata, Mitsuhiro

    2004-12-01

    Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and

  14. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode

    Energy Technology Data Exchange (ETDEWEB)

    Wray, S.; Grant, P.; Gainer, H. (National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA))

    1989-10-01

    In situ hybridization histochemistry and immunocytochemistry were used to study the prenatal expression of luteinizing hormone-releasing hormone (LHRH) cells in the mouse. Cells expressing LHRH mRNA and peptide product were first detected on embryonic day 11.5 (E11.5) in the olfactory pit. On E12.5, the majority of LHRH cells were located on tracks extending from the olfactory pit to the base of the telencephalon. From E12.5 to E15.5, LHRH cells were detected in a rostral-to-caudal gradient in forebrain areas. Prior to E12.5, cells expressing LHRH mRNA were not detected in forebrain areas known to contain LHRH cells in postnatal animals. Quantitation of cells expressing LHRH mRNA showed that the number of labeled cells on E12.5 (approximately 800) equaled the number of LHRH cells in postnatal animals, but more than 90% of these cells were located in nasal regions. Between E12.5 and E15.5, the location of LHRH cells shifted. The number of LHRH cells in the forebrain increased, while the number of LHRH cells in nasal regions decreased over this same period. These findings establish that cells first found in the olfactory pit and thereafter in forebrain areas express the LHRH gene and correspond to the position of LHRH immunopositive cells found at these developmental times. To further examine the ontogeny of the LHRH system, immunocytochemistry in combination with (3H)thymidine autoradiography was used to determine when LHRH cells left the mitotic cycle. We show that LHRH neurons exhibit a discrete time of birth, suggesting that they arise as a single neuronal population between E10.0 and E11.0. Postnatal LHRH neurons were birth-dated shortly after differentiation of the olfactory placode and before LHRH mRNA was expressed in cells in the olfactory pit.

  15. 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.

  16. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    Science.gov (United States)

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

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

    Science.gov (United States)

    Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta

    2017-01-01

    Summary 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. Learning points: Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly. Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion

  18. Noradrenergic regulation of hypothalamic cells that produce growth hormone-releasing hormone and somatostatin and the effect of altered adiposity in sheep.

    Science.gov (United States)

    Iqbal, J; Manley, T R; Yue, Q; Namavar, M R; Clarke, I J

    2005-06-01

    The growth hormone (GH) axis is sensitive to alteration in body weight and there is evidence that central noradrenergic systems regulate neurones that produce growth hormone-releasing hormone (GHRH) and somatostatin (SRIF). This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights. We also studied the effects of altered body weight on expression of dopamine beta-hydroxylase (DBH), the enzyme that produces noradrenalin from dopamine. Ovariectomised ewes were made Lean (39.6 +/- 2.6 kg; Mean +/- SEM) by dietary restriction, whereas Normally Fed animals (61.2 +/- 0.8 kg) were maintained on a regular diet. Brains were perfused for immunohistochemistry and in situ hybridisation. The Mean +/- SEM number of GHRH-immunoreactive (-IR) cells was lower in Normally Fed (65 +/- 7) than in Lean (115 +/- 14) animals, whereas the number of SRIF-IR cells was similar in the two groups (Normally Fed, 196 +/- 17; Lean 230 +/- 21). Confocal microscopic analysis revealed that the percentage of GHRH-IR cells (Normally Fed 36 +/- 1.5% versus Lean 32 +/- 4.6%) and percentage of SRIF-IR cells (Normally Fed 30 +/- 40.4% versus Lean 32 +/- 2.3%) contacted by noradrenergic fibres did not change with body weight. FluoroGold retrograde tracer injections confirmed that noradrenergic projections to the arcuate nucleus are from ventrolateral medulla and noradrenergic projections to periventricular nucleus arise from the ventrolateral medulla, nucleus of solitary tract, locus coeruleus (LC) and the parabrachial nucleus (PBN). DBH expressing cells were identified using immunohistochemistry and in situ hybridisation and the level of expression (silver grains/cell) quantified by image analysis. The number of DBH cells was similar in Normally Fed and Lean animals, but the level of expression/cell was lower (P < 0.02) in the PBN and LC of Lean animals. These results provide an anatomical basis for the

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

    Science.gov (United States)

    Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta; Murray, Robert D

    2017-01-01

    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 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. Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly.Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion, mainly from neuroendocrine tumours of pancreatic or bronchial origin.Differentiating between acromegaly of pituitary origin and

  20. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bratton, G.R.; Hiney, J.K.; Dees, W.L. (Texas A M Univ., College Station, TX (United States))

    1994-01-01

    In the present study, the authors evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E[sub 2] (PGE[sub 2]) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O[sub 2]-5% CO[sub 2]. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 [mu]M. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 [mu]M norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE[sub 2] (2.8 [mu]M) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE[sub 2] released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE[sub 2]-induced release of LHRH. Additionally, Pb did not alter basal PGE[sub 2] release; however, it significantly blocked the NE-induced release of PGE[sub 2]. Since NE-induced LHRH release is mediated by PGE[sub 2], these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE[sub 2] synthesis/release within the ME, resulting in diminished LHRH secretion.

  1. Regular Yoga Practice Improves Antioxidant Status, Immune Function, and Stress Hormone Releases in Young Healthy People: A Randomized, Double-Blind, Controlled Pilot Study.

    Science.gov (United States)

    Lim, Sung-Ah; Cheong, Kwang-Jo

    2015-09-01

    The aim of the present study is to highlight the beneficial effects of yoga practice on bio-parameters, such as oxidative stress, antioxidant components, immune functions, and secretion of stress hormones, in healthy young people. This study was conducted on healthy volunteers recruited from among university students, who were divided into two groups: a control (no yoga intervention, n=13) group and a yoga (n=12) group. Yoga practice was with an instructor for 90 minutes once a week spread over 12 weeks, with recommendations to practice daily at home for 40 minutes with the help of a DVD. The yoga program consisted of yoga body poses (asanas), exercises involving awareness, voluntary regulation of breath (pranayama), and meditational practices. Whole blood samples were collected when the volunteers had fasted for 8 hours at 0 and 12 weeks. The oxidative stress/antioxidant components, immune-related cytokines, and stress hormones were evaluated in serum or plasma. Serum levels of nitric oxide, F2-isoprostane, and lipid peroxide were significantly decreased by yoga practice (pyoga practice compared with the control group (pYoga practice also significantly increased immune-related cytokines, such as interleukin-12, and interferon-γ, in serum (pYoga practice significantly reduced the plasma levels of adrenalin (pyoga practice remarkably attenuated oxidative stress and improved antioxidant levels of the body. Moreover, yoga beneficially affected stress hormone releases as well as partially improved immune function.

  2. Ligand-biased regulation of PtdIns(3,4,5)P3-dependent signal transduction in GPCR control of pituitary hormone release.

    Science.gov (United States)

    Pemberton, Joshua G; Chang, John P

    2016-12-01

    Biased signaling describes the selective activation of signal transduction cascades by structurally-related ligands downstream of shared G protein-coupled receptors (GPCRs). Although class I phosphoinositide 3-kinases (PI3Ks) are important components of GPCR-controlled transduction networks, little is known regarding the potential for biased regulation of class I PI3K-dependent signaling. The full compliment of class I PI3K catalytic subunits (p110α, p110β, p110δ and p110γ) first appear in bony fishes and, despite being associated with distinct cellular functions, all class I PI3Ks produce the lipid second-messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). We have previously shown that two endogenous gonadotropin-releasing hormones (GnRH2 and GnRH3), which both signal through shared Gαq/11-coupled receptors, selectively activate different subsets of class I PI3K isoforms in their control of hormone release from goldfish (Carassius auratus) pituitary cells. Here, we tested the hypothesis that the biased activation of class I PI3K isoforms results in the selective recruitment of PtdIns(3,4,5)P3-sensitive effectors downstream of GnRH-stabilized GPCRs using pharmacological mapping. Our results reveal that distinct PtdIns(3,4,5)P3-sensitive effectors are involved in the differential control of GnRH2- and GnRH3-stimulated, as well as basal, hormone release and implicate the participation of non-canonical PtdIns(3,4,5)P3-sensitive transduction elements. Furthermore, observations using a selective inhibitor of the shared Gβγ-effector interaction surface indicate a role for Gβγ-dependent signaling in the integrated control of pituitary hormone exocytosis. These novel findings add to our understanding of functional selectivity in GPCR signal transduction networks, in general, and reveal the complexity of biased signaling downstream of class I PI3K catalytic activity.

  3. 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

    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...... but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas...... on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic euglycemic clamp conditions with muscle biopsies and fat biopsies in each period during infusion with saline or LPS. RESULTS: LPS increased cortisol and growth hormone (GH) levels in CTR...

  4. Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

    Science.gov (United States)

    Cacabelos, R; Yamatodani, A; Fukui, H; Niigawa, H; Miyake, A; Watanabe, T; Nishimura, T; Wada, H

    1987-04-01

    Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.

  5. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  6. Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)

    1984-01-01

    The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

  7. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-11-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests.

  8. 腹腔注射LHRH-A对黑鲷生长激素及其受体的影响%Effects of Luteinizing Hormone-releasing Hormone Analogue Injection on Growth Hormone and Its Receptor in Black Seabream

    Institute of Scientific and Technical Information of China (English)

    邓利; 林浩然

    2003-01-01

    以海水硬骨鱼类黑鲷为研究对象,腹腔注射溶于生理盐水的促性腺激素,释放激素(gonadotropin-releasing hormone,GnRH)的类似物(analogue of luteinizing hormone- releasing hormone,LHRH-A),对照组注射生理盐水.24 h后注射LHRH-A组黑鲷血清生长激素(growth hormone,GH)水平显著高于对照组(p<0.05),于36 h又恢复到对照组水平.注射LHRH-A组肝脏生长激素受体(growth hormone receptor,GHR)及GHR mRNA均与对照组无显著差异.结果表明,腹腔注射LHRH-A刺激了处于性腺成熟期黑鲷GH的分泌,但对黑鲷肝脏GHR及其基因表达无明显影响.

  9. 聚乙二醇化生长激素释放激素的研究进展%The research of development on Pegylation of growth hormone-releasing hormone

    Institute of Scientific and Technical Information of China (English)

    王永; 刘沐荣; 万海同

    2012-01-01

    生长激素释放激素(growth hormone-releasing hormone,GHRH)又称生长激素释放因子(growth hormone-releasing factor,GRF),是由下丘脑分泌的一种肽类激素,具有促进垂体促生长素细胞合成和释放生长激素(growth hormone,GH)的作用,临床上可以用来治疗矮小症、HIV相关的脂肪营养不良、代谢综合征、艾滋病、创伤等疾病.然而GHRH应用到临床上的最大不足就是体内半衰期比较短(一般10~20 min).为了延长GHRH在体内的半衰期,减少频繁用药给患者带来的不适,须对GHRH进行修饰,以期达到半衰期显著延长,免疫原性有所降低.为此,本文主要综述了GHRH以及GHRH长效修饰的研究进展,尤其是PEG修饰GHRH的最新进展.

  10. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly.

    OpenAIRE

    Frohman, L A; Szabo, M; Berelowitz, M.; Stachura, M E

    1980-01-01

    Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amount...

  11. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study.

    Science.gov (United States)

    Pedersen, Camilla; Lefevre, Solenne; Peters, Véronique; Patterson, Michael; Ghatei, Mohammad A; Morgan, Linda M; Frost, Gary S

    2013-07-01

    Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would augment the release of anorectic gut hormones and reduce appetite consistently in non-obese humans. Twelve non-obese participants were recruited for a 5-week dose-escalation study. Following a 9-14-day run-in, participants increased their daily oligofructose intake every week from 15, 25, 35, 45, to 55 g daily. Subjective appetite and side effects were monitored daily. Three-day food diaries were completed every week. Appetite study sessions explored the acute effects of 0, 15, 35, and 55 g oligofructose on appetite-related hormones, glycaemia, subjective appetite, and energy intake. In the home environment, oligofructose suppressed hunger, but did not affect energy intake. Oligofructose dose-dependently increased peptide YY, decreased pancreatic polypeptide and tended to decrease ghrelin, but did not significantly affect appetite profile, energy intake, glucose, insulin, or glucagon-like peptide 1 concentrations during appetite study sessions. In conclusion, oligofructose supplementation at ≥ 35 g/day increased peptide YY and suppressed pancreatic polypeptide and hunger; however, energy intake did not change significantly.

  12. 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.

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

    Science.gov (United States)

    Bach, Ermina; Møller, Andreas B; Jørgensen, Jens O L; Vendelbo, Mikkel H; Jessen, Niels; Pedersen, Steen B; Nielsen, Thomas S; Møller, Niels

    2016-11-01

    Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses). Single-blind randomized. We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic-euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS. LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3-fold) and decreased palmitate-specific activity (SA) 40-50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups. LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS. © 2016 European Society of Endocrinology.

  14. Growth hormone release from chicken anterior pituitary cells in primary culture: TRH and hpGRF synergy, protein synthesis, and cyclic adenosine 3'5'-monophosphate.

    Science.gov (United States)

    Perez, F M; Malamed, S; Scanes, C G

    1989-01-01

    Our earlier work showed that the effects of thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) on growth hormone (GH) release are synergistic (greater than additive) in a primary culture of chicken adenohypophyseal cells. The purpose of the present studies was to investigate the possible participation of protein synthesis and cyclic adenosine 3'5'-monophosphate (cAMP) in GH release. Following culture (48 hr), cells were incubated for 2 hr with test agents. Cycloheximide (an inhibitor of protein synthesis) had no effect on basal (absence of test agent) GH release or hpGRF-induced GH release. However, cycloheximide abolished the synergy between TRH and hpGRF. Although neither TRH nor hpGRF alone stimulated GH production (intracellular GH plus GH release) during a 2-hr incubation period, in combination these secretagogues increased total GH. These findings suggest that GH release from the chicken somatotroph under conditions of TRH and hpGRF synergy requires protein synthesis. In other studies, cells were exposed to agents inducing the formation of cAMP and either TRH or hpGRF. 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX; 10(-3) M) alone stimulated GH release to values between 30 and 50% over the basal value. The combined effects of each of these agents and TRH on GH release were synergistic. Similarly, IBMX and hpGRF exerted synergistic effects on GH release. In contrast, no synergy was shown between hpGRF and either 8 Br-cAMP or forskolin; their combined actions were less than additive.

  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. 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.

  17. [Role of estrogen-sensitive neurons in the arcuate region of the hypothalamus in the mechanism of luteinizing hormone release].

    Science.gov (United States)

    Babichev, V N; Ignatkov, V Ia

    1978-01-01

    Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.

  18. Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness.

    Science.gov (United States)

    Louge, Pierre; Coulange, Mathieu; Beneton, Frederic; Gempp, Emmanuel; Le Pennetier, Olivier; Algoud, Maxime; Dubourg, Lorene; Naibo, Pierre; Marlinge, Marion; Michelet, Pierre; Vairo, Donato; Kipson, Nathalie; Kerbaul, François; Jammes, Yves; Jones, Ian M; Steinberg, Jean-Guillaume; Ruf, Jean; Guieu, Régis; Boussuges, Alain; Fenouillet, Emmanuel

    2016-06-01

    Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high

  19. Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release.

    Directory of Open Access Journals (Sweden)

    Nora Prochnow

    Full Text Available Harmful effects of electromagnetic fields (EMF on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF signals of the Universal Mobile Telecommunications System (UMTS to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH and on hippocampal derived synaptic long-term plasticity (LTP and depression (LTD as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg. The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg cannot be excluded.

  20. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    Energy Technology Data Exchange (ETDEWEB)

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-03-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses.

  1. Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity. Part 2; Hypothalamic Growth Hormone-Releasing Factor, Somatostatin Immunoreactivity, and Messenger RNA Levels in Microgravity

    Science.gov (United States)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1994-01-01

    Immunohistochemical analyses of hypothalamic hormones carried out on tissue from rats flown on an earlier flight (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. We found that staining in the median eminence for peptides that provide both stimulatory (growth hormone-releasing factor, or GRF) and inhibitory (somatostatin, SS) influences on growth hormone secretion were depressed in flight animals relative to synchronous controls, while staining for other neuroendocrine peptides, cortocotropin-releasing factor and arginine vasopressin, were similar in these two groups. While this suggests some selective impact of weightlessness on the two principal central nervous system regulators of growth hormone dynamics, the fact that both GRF- and SS-immunoreactivity (IR) appeared affected in the same direction is somewhat problematic, and makes tentative any intimation that effects on CNS control mechanisms may be etiologically significant contributors to the sequelae of reduced growth hormone secretion seen in prolonged space flight. To provide an additional, and more penetrating, analysis we attempted in hypothalamic material harvested from animals flown on Cosmos 2044 to complement immunohistochemical analyses of GRF and SS staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

  2. Effects of growth hormone-releasing hormone treatment on milk production and plasma hormones and metabolites in lactating Japanese Black cows under negative energy balance.

    Science.gov (United States)

    Shingu, H; Hodate, K; Kushibiki, S; Touno, E; Oshibe, A; Ueda, Y; Shinoda, M; Ohashi, S

    2009-04-01

    The current study was performed to clarify the effects of GHRH treatment on milk production and plasma hormones and metabolites in lactating Japanese Black cows (a beef breed) under negative energy balance (EB). Ten multiparous lactating beef cows were offered a normal-energy diet daily (110% of ME requirements for maintenance and lactation) until 5 d in milk (DIM) to standardize the cows before dietary treatment. From 6 DIM to the final days (63 DIM) of the experiment, the cows were allotted to experimental dietary treatments: 5 cows were offered a diet formulated for 130% [high-energy diet (HED)] and the remaining 5 cows were offered a diet formulated for 80% [low-energy diet (LED)] of ME requirements for maintenance and lactation. In addition, all cows received daily subcutaneous injections of 3 mg of bovine GHRH from 36 to 56 DIM (GHRH treatment period). Differences in BW of HED- and LED-fed cows at 63 DIM were +28.4 and -7.2 kg compared with BW at 6 DIM, and HED- and LED-fed cows were under positive EB (+23.7 MJ/d) and negative EB (-11.6 MJ/d) throughout the experiment period. Treatment with GHRH increased (Pnegative EB in lactating beef cows.

  3. Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse.

    Science.gov (United States)

    Frohman, M A; Downs, T R; Chomczynski, P; Frohman, L A

    1989-10-01

    We have isolated and cloned the full length cDNA for mouse GH-releasing hormone (mGRH) from mouse hypothalamus using a recently described strategy involving the polymerase chain reaction technique (PCR). Degenerate oligonucleotide primers were selected based on short (six amino acids) conserved regions in the human and rat GRH peptides that would recognize DNA sequences encoding similar amino acids regardless of codon usage. Primer-extended cDNA was amplified by PCR on cDNA templates prepared by reverse transcribing total mouse hypothalamic RNA. After cloning and sequencing the initial product, the 3' and 5' ends of mGRH were generated using a separate PCR strategy (RACE protocol). The mGRH cDNA encodes a 103-amino acid reading frame, structurally similar to the human and rat GRH genes, containing a signal sequence, a 42-residue GRH peptide, and a 31-residue C-terminal region. Although the structures of mouse and rat GRH are highly conserved in the signal peptide and C-terminal region, there is considerable diversity in the GRH region, which exhibits nearly comparable homology with the rat (68%) and human (62%) structures. Differences between mouse and rat GRH were also found in the amino acid cleavage sites at the 5' and 3' ends of the mature peptide and at the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    QIU Wen-cai; WANG Zhi-gang; WANG Wei-gang; YAN Jun; ZHENG Qi

    2008-01-01

    Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment.In normal animals,both ghrelin and its synthetic peptide,growth hormone releasing peptide 6(GHRP-6),increase gastric emptying.Thus,we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.Methods A diabetic guinea pig model was produced by intraperitoneal(i.p.)injection of streptozotocin(STZ,280 mg/kg).Diabetic guinea pigs were injected i.p.with ghrelin or GHRP-6(10-100 pg/kg),and the effects on gastric emptying were measured after intragastric application of phenol red.The effect of atropine or a growth hormone secretagogue receptor(GHS-R)antagonist,D-Lys3-GHRP-6,on the gastroprokinetic effects of ghrelin or GHRP-6(100 μg/kg)was also investigated.Further,the in vitro effects of ghrelin or GHRP-6(0.01-10 μmol/L)on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined.Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction(RT-PCR).Results We established a guinea pig model of delayed gastric emptying.Ghrelin(20,50,or 100 μg/kg)and GHRP-6 (20,50,or 1 00 μg/kg)accelerated gastric emptying in diabetic guinea pigs with gastroparesis(n=-6,P<0.05).In the presence of atropine,which delayed gastric emptying,ghrelin and GHRP-6(100 μg/kg)failed to accelerate gastric emptying(n=6,P<0.05).D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist(n=6,P<0.05).Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs(n=6,P<0.05).RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis,potentially,by activating the

  5. β-Hydroxybutyric acid inhibits growth hormone-releasing hormone synthesis and secretion through the GPR109A/extracellular signal-regulated 1/2 signalling pathway in the hypothalamus.

    Science.gov (United States)

    Fu, S-P; Liu, B-R; Wang, J-F; Xue, W-J; Liu, H-M; Zeng, Y-L; Huang, B-X; Li, S-N; Lv, Q-K; Wang, W; Liu, J-X

    2015-03-01

    β-Hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA-mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone-releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = -0.89, P hypothalamus in both in vivo and in vitro, and this effect was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated the extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) kinases, as shown by western blot analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA-mediated reduction in Gsh-1 expression and GHRH synthesis and secretion. These results strongly suggest that BHBA directly regulates GHRH synthesis and secretion via the GPR109A/ERK1/2 MAPK pathway, and also that Gsh-1 is essential for this function. © 2015 British Society for Neuroendocrinology.

  6. Effect of growth hormone-releasing peptide on ardiac cholinergic nerve fiber density distribution in a rat model of heart failure

    Institute of Scientific and Technical Information of China (English)

    Guozhong Tian; Xiuqin Ni; Yong Zhao; Jia Feng; Yanjun Li; Zhenya Zhong; Shuling Bai

    2009-01-01

    BACKGROUND: Changes in the cardiac autonomic nerve are considered to be important factors in the mechanisms of heart failure. It is possible to reduce or slow down nerve degeneration and necrosis, provided that patients take effective neuroprotectants during the early stages of heart failure. Moreover, it is possible to relieve the pathological process and reduce the risk of death.OBJECTIVE: To study the effect of growth hormone releasing peptide (GHRP) on cardiac cholinergic nerve fiber density distribution in a rat model of heart failure, and verify whether GHRP can ameliorate denervation.DESIGN, TIME AND SETTING: A randomized controlled study was performed at the Key Laboratory of Anatomy, Harbin Medical University, between June and October 2009.MATERIALS: Fifty adult, healthy, female, Wistar rats, weighing (200±20) g, were randomly divided into GHRP (n=30), model (n=10), and sham operation (n=10) groups. GHRP-2 was made in Shanghai, China (batch No. z071212-03).METHODS: Acute myocardial infarction was established by ligating the left anterior descending coronary artery in the GHRP and model groups. Five weeks later, myocardial function was detected using color ultrasound electrocardiograph. Ejection fraction < 60% was considered to be a successful marker of chronic heart failure models. However, the left anterior descending coronary artery was not ligated in the sham operation group. The GHRP group was injected with 100μg/kg GHRP-2, and the other two groups were injected with the same volume of physiological saline, once per day.MAIN OUTCOME MEASURES: After 4 weeks, pathological changes in cardiac cholinergic nerve fibers were detected under optic microscopy following hematoxylin/eosin staining. In addition, density distribution was measured using a multi-function color pathological image system.RESULTS: In the sham operation group, myocardial cells were regular, uniformly stained, and no inflammatory cells were present. In the model group, myocardial cells

  7. 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...... (IL)-8, in the pathogenesis of growth hormone (GH) producing tumours.......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...

  8. 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...

  9. Leptin alters the response of the growth hormone releasing factor- growth hormone--insulin-like growth factor-I axis to fasting.

    Science.gov (United States)

    LaPaglia, N; Steiner, J; Kirsteins, L; Emanuele, M; Emanuele, N

    1998-10-01

    Proper nutritional status is critical for maintaining growth and metabolic function, playing an intimate role in neuroendocrine regulation. Leptin, the recently identified product of the obese gene, may very well be an integral signal which regulates neuroendocrine responses in times of food deprivation. The present study examines leptin's ability to regulate hormonal synthesis and secretion within the GRF-GH-IGF axis in the adult male rat during almost 3 days of fasting. Serum levels of GH and IGF-I were drastically suppressed by fasting. Daily leptin administration was able to fully prevent the fasting-induced fall in serum GH. Leptin failed to restore IGF-I to control levels, however, suggesting possible GH resistance. Fasting caused an insignificant increase in GH mRNA, while leptin injections significantly increased steady-state levels of this message. The GRF receptor (GRFr) message was not altered with fasting or leptin treatment. Leptin also exhibited effects at the hypothalamic level. Fasting induced a sharp fall in GRF mRNA expression and leptin injections partially prevented this fall. However, there were no observed changes in the hypothalamic GRF content. These results provide evidence that leptin may function as a neuromodulator of the GRF-GH-IGF axis communicating to this hormonal system the nutritional status of the animal.

  10. 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.

  11. Differential sensitivity of growth hormone-releasing hormone and somatostatin release from perifused mouse hypothalamic fragments in response to glucose deficiency.

    Science.gov (United States)

    Sato, M; Frohman, L A

    1993-06-01

    The effects of glucose deficiency on growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) release from mouse hypothalamic fragments were investigated using an in vitro perifusion system. Fragments were perifused with Krebs-Ringer bicarbonate solution (KRB) containing 5.6 mM glucose for 3 h followed by reduced glucose concentrations in KRB for the next 2 h. GRH release was simulated by 0.7-2.8 mM glucose in an inverse concentration-dependent manner. In contrast, SRIH release was not stimulated by glucose at concentrations of 2.8 and 1.4 mM; only at 0.7 mM was there a modest stimulation of SRIH release that was comparable to the effect of 2.8 mM glucose on GRH release. The maximal stimulation of GRH and SRIH release by 0.7 mM glucose was 221 and 150%, respectively, of controls. Glucose concentrations of 11.2 and 22.4 mM inhibited GRH release but did not alter SRIH release. The glucose analog 2-deoxy-D-glucose (2-DG; 5.6-39.2 mM) also stimulated GRH release in a dose-dependent manner, and SRIH release was less sensitive to 2-DG than was GRH. The maximal stimulation of GRH and SRIH release by 39.2 mM 2-DG was 190 and 147%, respectively, of controls. Increases in GRH and SRIH release stimulated by 30 mM KCl 1 h after exposure to low glucose or 2-DG were not significantly different from those after exposure to 5.6 mM glucose. However, the SRIH response to K(+)-induced depolarization was much greater than that of GRH. The glucose intermediate pyruvate (4.9 and 9.8 mM) partially inhibited both GRH and SRIH release induced by 0.7 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. 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...

  13. 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...... (30 mg/day for 1 and 3 days). However, peak GH-responses to PD in combination with GHRH were reduced during HC (80 mg/day for 1 day) compared to no glucocorticoid pretreatment in all patients. Short-term hypocortisolism did not significantly affect peak GH-responses. CONCLUSION: The GH...

  14. Características testiculares de touros imunizados com vacina anti-hormônio liberador do hormônio luteinizante Testicular characteristics of bulls immunosterilized with anti-luteinizing hormone-releasing hormone vaccine

    Directory of Open Access Journals (Sweden)

    Ricardo Zanella

    2009-10-01

    Full Text Available O objetivo deste trabalho foi avaliar a ação imunoesterilizadora de uma vacina anti-hormônio liberador de hormônio luteinizante (LHRH, composta por ovalbumina-LHRH-7 e tiorredoxina-LHRH-7, em touros mestiços Nelore. Vinte e seis touros, com dois anos de idade, foram distribuídos aleatoriamente em dois grupos de 13 animais. No grupo I, os animais receberam uma dose e dois reforços da vacina nos dias 0, 141, e 287 do experimento. No grupo II, os animais não receberam nenhum tratamento (controle. Para avaliar o efeito da vacina nos touros, foi realizada a mensuração da circunferência escrotal no início do experimento e no dia do abate, 741 dias depois. Por ocasião do abate, também foi coletada uma amostra dos testículos para avaliação histológica. O grupo imunizado apresentou circunferência escrotal ao abate de 22±5,98 cm, menor do que a do grupo controle que foi de 35,6±2,4 cm. Na análise histológica dos animais do grupo imunizado, foi observada degeneração testicular com ausência de espermatozoides em 85% dos animais avaliados, os outros 15% apresentaram redução no número de espermatozoides, em comparação aos animais do grupo controle. A vacina anti-LHRH, com fusão de proteínas, é efetiva na castração imunológica de touros e deve ser considerada como alternativa para utilização na produção bovina extensiva no Brasil.The objective of this study was to evaluate the immunosterilization action of the anti-luteinizing hormone-releasing hormone (LHRH vaccine, composed with ovalbumin-LHRH-7 and thioredoxin-LHRH-7, in Nelore-cross bulls. Twenty-six 2-year old bulls were randomly assigned in two groups of 13 animals each. The animals of group I received a primary and two booster injections of the vaccine on days 0, 141, and 287 of the experiment. In group II, the control group, the bulls did not receive any type of treatment. Scrotal circumference was measured in the beginning of the experiment and at slaughter

  15. Butyrate Increases Intracellular Calcium Levels and Enhances Growth Hormone Release from Rat Anterior Pituitary Cells via the G-Protein-Coupled Receptors GPR41 and 43

    OpenAIRE

    Maria Consolata Miletta; Vibor Petkovic; Andrée Eblé; Ammann, Roland A; Flück, Christa E.; Primus-E Mullis

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous...

  16. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43

    OpenAIRE

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Ammann, Roland; Flück, Christa; Mullis, Primus-Eugen

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous...

  17. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Directory of Open Access Journals (Sweden)

    Maria Consolata Miletta

    Full Text Available Butyrate is a short-chain fatty acid (SCFA closely related to the ketone body ß-hydroxybutyrate (BHB, which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR, GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  18. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Science.gov (United States)

    Miletta, Maria Consolata; Petkovic, Vibor; Eblé, Andrée; Ammann, Roland A; Flück, Christa E; Mullis, Primus-E

    2014-01-01

    Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR), GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH)-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  19. Effect of a hormone-releasing intrauterine system (Mirena® on aromatase and Cox-2 expression in patients with adenomyosis submitted or not, to endometrial resection

    Directory of Open Access Journals (Sweden)

    Maia R

    2012-04-01

    Full Text Available Hugo Maia Jr1,2, Clarice Haddad1, Julio Casoy1, Rebeca Maia1, Nathanael Pinheiro3, Elsimar M Coutinho11Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH, 2Itaigara Memorial Day Hospital, 3IMAGEPAT, Salvador, Bahia, BrazilObjective: To investigate the effect of a levonorgestrel-releasing intrauterine system (Mirena® on aromatase and cyclooxygenase-2 (Cox-2 expression in the endometrium of patients with adenomyosis who were submitted to endometrial resection at the time of insertion, compared to a group not submitted to endometrial resection and a group of controls with adenomyosis not submitted to any previous hormonal treatment.Patients and methods: Patients with adenomyosis (n = 89 were included in this study. Twenty-two patients had been using Mirena® for 5 years but had not been submitted to endometrial resection prior to insertion of the device. Twenty-four patients were submitted to endometrial resection at the time of Mirena® insertion. The remaining 43 patients with adenomyosis had undergone no previous hormonal treatment and served as a control group. Cox-2 and aromatase expression were determined in the endometrium by immunohistochemistry.Results: Use of Mirena® for 5 years reduced aromatase expression in the endometrium; however, this reduction was significantly greater in the uteri previously submitted to endometrial resection. The reduction in Cox-2 expression was significant only in the uteri submitted to endometrial resection followed by the insertion of Mirena®.Conclusion: Endometrial resection followed by the insertion of Mirena® was associated with greater rates of amenorrhea in patients with adenomyosis, which in turn were associated with a more effective inhibition of aromatase and Cox-2 expression in the endometrium.Keywords: aromatase, Mirena®, adenomyosis, Cox-2, endometrium, levonorgestrel

  20. Parenteral versus early intrajejunal nutrition: Effect on pancreatitic natural course, entero-hormones release and its efficacy on dogs with acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Huan-Long Qin; Zhen-Dong Su; Lei-Guang Hu; Zai-Xian Ding; Qing-Tian Lin

    2003-01-01

    AIM: To evaluate the effect of early intrajejunal nutrition (EIN) on the natural course, entero-hormone secretion and its efficacy on dogs with acute pancreatitis.METHODS: An acute pancreatitis model was induced by injecting 1 ml/kg of combined solution (2.5% sodium taurocholate and 8 000-10 000 BAEE units trypsin/mi) into the pancreas via pancreatic duct. Fifteen dogs were divided into parenteral nutrition (PN) group and EIN group. Two groups were isonitrogenous and isocaloric. EIN was used at postoperative 24 h. Serum glucose, calcium, amylase and lysosomal enzymes were determined before and 1, 4, 7 d after acute pancreatitis was induced. All the dogs were injected 50 uCi 125I-BSA 4 h before sacrificed on the 7th day.The 125I -BSA index of the pancreas/muscle, pancreas/blood,and pancreas pathology score (PPS) were determined. The peripheral plasma cholecystokinin (CCK), secretin (SEC) and gastrin were measured by ELISA and RIA, and was quantitative analysis of pancreatic juice and amylase,pancreatolipase and HCO3-, Cl-, Na+ and K+ performed by an autochemical analyzer at 30, 60, 120 and 180 min after beginning PN or EIN on the first day.RESULTS: There was no difference between two groups in the contents of serum calcium, amylase and lysosomal enzymes, 125I-BSA index of pancreas/muscle and pancreas/blood and PPS. The contents of CCK and gastrin in EIN were higher than those in PN group at 60 and 120 min (P<0.05).The content of SEC post-infusion of nutrition solution was higher than that of pre-infusion of nutrition solution in both groups, and only at 60 min SEC in EIN group was higher than that in PN group. The content of gastrin in EIN was higher than that in PN group at 120 and 180 min (P<0.05).The changes of pancreatic juice, amylase, pancreatolipase and HCO3-, Cl-, Na+ and K+ between two groups did not reach significantly statistical difference (P>0.05).CONCLUSION: EIN does not stimulate entero-hormone and pancreatic juice secretion, and enzyme

  1. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    Science.gov (United States)

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  2. Heterogeneity of rat FSH by chromatofocusing: studies on serum FSH, hormone released in vitro and metabolic clearance rates of its various forms.

    Science.gov (United States)

    Blum, W F; Gupta, D

    1985-04-01

    Rat pituitary FSH was fractionated by chromatofocusing between pH 6 and 3. Ten components were resolved having apparent isoelectric points between 3.1 and 5.1. A comparative study of pituitary FSH and FSH secreted in vitro by quartered pituitary glands in the presence and in the absence of gonadotrophin-releasing hormone (GnRH) revealed similar patterns of charged species of intracellular and released FSH. Although GnRH increased FSH secretion about fourfold, no influence on the pattern of charged species was observed. Utilizing exclusion chromatography and chromatofocusing, pituitary FSH was compared to serum FSH which had been extracted by immuno-affinity chromatography. The results demonstrate for serum FSH a larger molecular size and a relative shift to more acidic components. Metabolic clearance rates of eight FSH components separated by chromatofocusing were measured in adult male rats. Half-lives varied between 13 min and several hours. A correlation existed between decrease of isoelectric points and decrease of metabolic clearance rates. These findings suggest that all hypophysial FSH components are secreted into the circulation at similar rates and the more acidic FSH components which appear to contain increased sialic acid, have a longer circulatory half-life and are more abundant in serum. It is concluded that sialylation may be involved in modulating serum FSH levels.

  3. Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin.

    Directory of Open Access Journals (Sweden)

    Lara Pena-Bello

    Full Text Available Metabolic substrates and nutritional status play a major role in growth hormone (GH secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG administration in normal and obese patients is a pending issue.The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity.We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed.The AUC of GH (μg/L•min was lower in obese (249.8±41.8 than in healthy women (490.4±74.6, P=0.001. The AUC of total ghrelin (pg/mL•min was lower in obese (240995.5±11094.2 than in healthy women (340797.5±37757.5, P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.

  4. Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices.

    Science.gov (United States)

    Glanowska, Katarzyna M; Venton, B Jill; Moenter, Suzanne M

    2012-10-17

    Pulsatile gonadotropin-releasing hormone (GnRH) release is critical for the central regulation of fertility. There is no method allowing real-time GnRH detection in brain slices. We developed fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFME) to detect GnRH release and validated it using a biologically relevant system. FSCV parameters (holding potential, switching potential, and scan rate) were determined for stable GnRH detection in vitro, then optimized for GnRH detection in mouse brain slices. Placement of CFMEs in the median eminence (ME) near GnRH terminals allowed detection of both KCl-evoked and spontaneous GnRH release. GnRH release was also detected from GnRH fibers passing near GnRH soma and near fiber-fiber appositions in the preoptic area. No GnRH signal was detected from CFMEs in the ME of hpg mice, which lack GnRH, or in regions not containing GnRH neurons in wild-type mice; application of exogenous GnRH produced a signal similar to that observed for spontaneous/evoked endogenous GnRH release. Using an established mouse model that produces diurnal variations in GnRH neuron activity, we demonstrated corresponding changes in spontaneous GnRH release in the median eminence. These results validate FSCV to detect GnRH in brain slices and provide new information on the sites and amounts of GnRH release, providing insight into its neuromodulatory functions.

  5. Different effects of growth hormone-releasing hormone (GRH) and somatostatin on growth hormone and stable metabolite of prostaglandin E2, 13, 14-dihydro-15-keto-prostaglandin E2 (PGE2-M) in normal subjects.

    Science.gov (United States)

    Zacharieva, S; Muchá, I; Popova, J; Andonova, K

    1992-01-01

    Twenty four healthy subjects were placed in two treatment groups: 1. The first group consisted of twelve subjects in whom growth releasing hormone (GRH) (1 microgram/kg.BW) resulted in a marked and sustained elevation of serum growth hormone (GH) and a slight and delayed increase in plasma prostaglandin E2-M. In the second group, consisting also of twelve subjects, somatostatin infusion (500 micrograms/250 ml) was initiated and maintained for 60 min. Serum GH significantly decreased at 30 and 60 min during infusion and 15 min thereafter. We did not observe any changes in plasma prostaglandin E2-M during or after somatostatin infusion. The results obtained confirm previous in vitro studies and suggest a possible link between growth releasing hormone and prostaglandin E2 in their action on growth hormone secretion. It seems that somatostatin does not play a role in the control of prostaglandin E2 release.

  6. Alterations of serum levels of three kinds of promote hormone releasing hormones in patients with fibromyalgia%纤维肌痛患者血清中三种促激素释放激素含量的改变

    Institute of Scientific and Technical Information of China (English)

    虞金霞; 陈贵海

    2011-01-01

    ObjectiveTo explore alterations of serum levels and clinical significance of corticotropin releasing hormone (CRH), thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) in patients with fibromyalgia (FM). Methods A total of 55 subjects participated in this study: 29 healthy volunteers and 26 patients with FM recruited from Department of Neurology, the First Affiliated Hospital of Anhui Medical University from June 2009 to October 2010. The depression rate was assessed by Hamilton Depression Rating Scale-17. ELISA was used for the detection of the serum levels of CRH, TRH and GnRH. Normal distribution quantitative data were described by the (-x) ± s and tested by independent sample t-test. Non-normal quantitative data were described by interquartile range and tested by independent Mann-Whitney. The diagnostic specificity and sensitivity of 3 kinds of hormones test were analyzed by receiver operator characteristic ( ROC ) curve, and the Spearman correlation was used for analysis of hormone levels and age, gender, tenderness, pain degree and depression severity. Results Compared with the control (70. 0(48.7,78.0) ng/L), the fibromyalgia patients had obviously increased CRH (271.9 (210.9,326.5) rg/L, x2 =6.408, P<0. 01) , and significantly higher TRH ((82.7 ±6. 9 ) ng/L vs ( 87. 2 ± 6. 8 ) ng/L, t = 2. 560, P < 0. 05, respectively) and GnRH ( ( 18. 2 ± 0. 9 ) ng/L vs ( 19. 9 ± 1.6)ng/L,t =5. 324, P <0. 01, respectively). The serum concentrations of the CRH, TRH and GnRH were positively correlated with pain intensity and numbers of tenderness respectively, and those of the CRH and GnRH were positively correlated with depressive degree either. The areas under the ROC curve in the CRH, TRH and GnRH, evaluating the sensitivity and specificity for diagnosis of fibromyalgia, were respectively 1. 000, 0. 684 and 0. 854. Conclusions The FM patients had an increased secretion of CRH,TRH and GnRH. CRH might serve as the adjunctive criteria for

  7. Estrogen receptor immunoreactivity is present in the majority of central histaminergic neurons: evidence for a new neuroendocrine pathway associated with luteinizing hormone-releasing hormone-synthesizing neurons in rats and humans.

    Science.gov (United States)

    Fekete, C S; Strutton, P H; Cagampang, F R; Hrabovszky, E; Kalló, I; Shughrue, P J; Dobó, E; Mihály, E; Baranyi, L; Okada, H; Panula, P; Merchenthaler, I; Coen, C W; Liposits, Z S

    1999-09-01

    The central regulation of the preovulatory LH surge requires a complex sequence of interactions between neuronal systems that impinge on LH-releasing hormone (LHRH)-synthesizing neurons. The reported absence of estrogen receptors (ERs) in LHRH neurons indicates that estrogen-receptive neurons that are afferent to LHRH neurons are involved in mediating the effects of this steroid. We now present evidence indicating that central histaminergic neurons, exclusively located in the tuberomammillary complex of the caudal diencephalon, serve as an important relay in this system. Evaluation of this system revealed that 76% of histamine-synthesising neurons display ERalpha-immunoreactivity in their nucleus; furthermore histaminergic axons exhibit axo-dendritic and axo-somatic appositions onto LHRH neurons in both the rodent and the human brain. Our in vivo studies show that the intracerebroventricular administration of the histamine-1 (H1) receptor antagonist, mepyramine, but not the H2 receptor antagonist, ranitidine, can block the LH surge in ovariectomized estrogen-treated rats. These data are consistent with the hypothesis that the positive feedback effect of estrogen in the induction of the LH surge involves estrogen-receptive histamine-containing neurons in the tuberomammillary nucleus that relay the steroid signal to LHRH neurons via H1 receptors.

  8. Effects of antagonists of growth hormone-releasing hormone (GHRH) on GH and insulin-like growth factor I levels in transgenic mice overexpressing the human GHRH gene, an animal model of acromegaly.

    Science.gov (United States)

    Kovacs, M; Kineman, R D; Schally, A V; Zarandi, M; Groot, K; Frohman, L A

    1997-11-01

    Transgenic mice overexpressing the human GH-releasing hormone (hGHRH) gene, an animal model of acromegaly, were used to investigate the effects of potent GHRH antagonists MZ-4-71 and MZ-5-156 on the excessive GH and insulin-like growth factor I (IGF-I) secretion caused by overproduction of hGHRH. Because metallothionein (MT)-GHRH mice express the hGHRH transgene in various tissues, including the pituitary and hypothalamus, initial experiments focused on the effectiveness of the GHRH antagonists in blocking basal and stimulated GH secretion from pituitary cells in vitro. Both MZ-4-71 and MZ-5-156 suppressed basal release of GH from superfused MT-GHRH pituitary cells, apparently by blocking the action of endogenously produced hGHRH. In addition, these antagonists effectively eliminated the response to stimulatory action of exogenous hGHRH(1-29)NH2 (30 and 100 nM). To ascertain whether MZ-4-71 and MZ-5-156 could antagonize the effect of hGHRH hyperstimulation in vivo, each antagonist was administered to MT-GHRH transgenic mice in a single iv dose of 10-200 microg. Both compounds decreased serum GH levels in transgenic mice by 39-72% at 1 h after injection. The inhibitory effect of 50 microg MZ-5-156 was maintained for 5 h. Twice daily ip administration of 100 microg MZ-5-156 for 3 days suppressed the highly elevated serum GH and IGF-I concentrations in transgenic mice by 56.8% and 39.0%, respectively. This treatment also reduced IGF-I messenger RNA levels in the liver by 21.8% but did not affect the level of GH messenger RNA in the pituitary. Our results demonstrate that GHRH antagonists MZ-4-71 and MZ-5-156 can inhibit elevated GH levels caused by overproduction of hGHRH. The suppression of circulating GH concentrations induced by the antagonists seems to be physiologically relevant, because both IGF-I secretion and synthesis also were reduced. Our findings, showing the suppression of GH and IGF-I secretion with GHRH antagonists, suggest that this class of analogs

  9. Effects of leptin on gonadotropin-releasing hormone release from hypothalamic-infundibular explants and gonadotropin release from adenohypophyseal primary cell cultures: further evidence that fully nourished cattle are resistant to leptin.

    Science.gov (United States)

    Amstalden, M; Harms, P G; Welsh, T H; Randel, R D; Williams, G L

    2005-01-01

    In rodents and pigs, leptin stimulates the release of gonadotropin-releasing hormone (GnRH) from hypothalamus, gonadotropins from adenohypophyseal (AP) explants and cells, and luteinizing hormone (LH) from full-fed animals. In the current studies, we investigated whether leptin could stimulate the release of GnRH from bovine hypothalamic-infundibular (HYP) explants and gonadotropins from bovine adenohypophyseal cells. In Experiment 1A, HYP explants collected from 17 bulls and seven steers were incubated with Krebs-Ringer bicarbonate buffer (KRB) containing 0, 10, 100, or 1000 ng/ml recombinant ovine leptin (oleptin) for 30 min after a 3-h period of equilibration. None of the doses of leptin affected (P > 0.05) GnRH release into the media. In Experiment 1B, HYP explants collected from six steers were incubated with KRB containing 0 or 1000 ng/ml oleptin for two consecutive 30-min periods and challenged with 60 mM K(+) afterwards. Leptin did not affect (P > 0.05) basal or K(+)-stimulated release of GnRH. In Experiment 2, adenohypophyses from steers were collected at slaughter and cells dispersed and cultured for 4 days. On day 5, cells were treated with media alone (control) or media containing 10(-11), 10(-10), 10(-9), and 10(-8)M oleptin. Three independent replications were performed. None of the doses of leptin stimulated (P > 0.05) the release of LH. Although leptin at 10(-11), 10(-10), and 10(-9)M increased (P release of FSH compared to control-treated cells in one replicate, this effect was not confirmed in the other two replicates. Results support the hypothesis that leptin has limited effects on the release of GnRH and gonadotropins in full-fed cattle and reiterate important species differences in responsiveness to leptin.

  10. Ionic channels and hormone release from peptidergic nerve terminals.

    Science.gov (United States)

    Lemos, J R; Nordmann, J J

    1986-09-01

    Although there is considerable evidence that depolarization of nerve cell terminals leads to the entry of Ca2+ and to the secretion of neurohormones and neurotransmitters, the details of how ionic currents control the release of neuroactive substances from nerve terminals are unknown. The small size of most nerve terminals has precluded direct analysis of membrane ionic currents and their influence on secretion. We now report that it is possible, using patch-clamp techniques, to study stimulus--secretion coupling in isolated peptidergic nerve terminals. Sinus gland terminals from Cardisoma are easily isolated following collagenase treatment and appear morphologically and electrically very similar to non-dissociated nerve endings. We have observed two types of single-channel currents not previously described. The first ('f') channel is activated by intracellular Na+ and the second ('s') by intracellular Ca2+. Both show little selectivity between Na+ and K+. In symmetrical K+, these cation channels have mean conductances of 69 and 213 pS, respectively. Furthermore, at least three types of Ca2+ channels can be reconstituted from nerve terminal membranes prepared from sinus glands. Nerve terminals can also be isolated from the rat neural lobe. These neurosecretosomes release oxytocin and vasopressin, in response to membrane depolarization, only in the presence of external Ca2+. The depolarization of the nerve endings is associated with an increase in intracellular free Ca2+ concentration and this increase, measured using a fluorescent indicator, is abolished by Ca2+ channel blockers. Channels similar in their properties to the f and s channels also exist in rat neural lobe endings. Since these channels have not been found in other neurones or neuronal structures they may be unique to peptidergic nerve terminals.

  11. Effect of acute retrograde gastric electrical stimulation on gastric accommodation, emptying and gastrointestinal hormones releasing in obese patients%急性逆行胃电刺激对肥胖患者胃容受性、胃排空和胃肠激素释放的影响

    Institute of Scientific and Technical Information of China (English)

    房龙; 杜时雨; 姚树坤; 张艳丽; 李艳梅

    2011-01-01

    Objective To observe the effect of acute retrograde gastric electrical stimulation (RGES) on gastric accommodation,emptying and gastrointestinal hormones releasing in obese patients. Methods Sixteen obese patients were examined. On the first day,a pair of mucosal gastric electrodes was placed under endoscope. The liquid meal load test and the standard solid meal gastric emptying test were carried out on the second day. RGES was performed starting at 30 minutes before each test and through the whole testing process. The serum leptin,ghrelin,resistin and peptide YY were examined before and after the standard solid meal gastric emptying test. On the third day,sham stimulation was given. The effect of acute RGES on related index was compared by self-control.Results BMI of the 16 patients was (32. 90±2. 99) kg/m2. Acute RGES significantly reduced the liquid meal volume of fullness [(460±148) ml and (630±219) ml,t=-7. 200,P<0. 01] and the maximal tolerable meal volume [(699±215) ml and (926±295) ml,t=- 5. 390,P<0. 01]. The effects of RGES and sham RGES on half-emptying time of standard solid meal was (109±26) min and (103±31) min (t=1. 009,P= 0. 329);on the retention rate of standard solid meal at one hour and two hour was (63. 37±9. 75)% and (59. 73±12.87)% (t=1. 834,P= 0. 087),(42.22±13.97)%and (38. 33±16. 87)% (t= 1.780,P= 0. 095),respectively. The ratio of gastrointestinal hormones after and before the stimulation also of the sham stimulation,leptin was 1. 03±0. 34 and 1. 08±0. 38(t=-0.386,P=0. 705),ghrelin was 0. 99±0. 11 and 0. 98±0. 12 (t= 0. 413,P=0.685),resistin was 1. 11±0. 25 and 0. 99±0. 24 (t= 1. 753,P= 0. 100),and peptide YY was 1. 56±0. 71 and 1. 33±0. 61 (t=1. 402,P= 0. 181). Conclusions In obese patients,acute RGES significantly reduce the liquid meal volume by lower gastric accommodation,to certain extent which will delay gastric emptying. There is no significant influence on gastrointestinal hormones releasing.%目的 观察急

  12. 促性腺激素释放激素及多巴胺对斜带石斑鱼生长激素分泌及其mRNA表达的调控%Stimulatory effects of gonadotropin-releasing hormone and dopamine on growth hormone release and growth hormone mRNA expression in Epinephelus coioides

    Institute of Scientific and Technical Information of China (English)

    冉雪琴; 李文笙; 林浩然

    2004-01-01

    研究斜带石斑鱼生长激素分泌及其mRNA表达的调控规律对于性别分化的控制、临床药物的选择,以及石斑鱼的增养殖等均具有重要的理论意义和实践意义.本文应用静态孵育系统,采用放射免疫测定法和化学发光液相杂交实验,研究GnRH和DA对斜带石斑鱼GH分泌、GH mRNA合成的调控作用.100 nmol/L sGnRH作用斜带石斑鱼脑垂体碎片1~24 h,明显促进GH的释放和GH mRNA的合成,并具有时间依存性;10 nmol/L~1μmol/L sGnRH作用1 h能明显促进斜带石斑鱼脑垂体释放GH,促进GH mRNA的合成,表现出明显的剂量效应.100 nmol/L、1μmol/L mGnRH作用1 h以一定的剂量依存方式促进GH的释放、促进GH mRNA的合成,但mGnRH的效应比相应剂量的sGnRH的作用弱.APO为DA受体的非选择性激动剂,不同剂量APO对斜带石斑鱼脑垂体碎片的作用结果显示,10 nmol/L~lμmol/L APO以剂量依存方式促进斜带石斑鱼脑垂体碎片释放GH、促进GH mRNA的合成;1μmol/L APO作用12 h以上明显促进GH的释放和GH mRNA的合成,并随时间的延长而增加.与sGnRH对斜带石斑鱼GH释放、GH mRNA合成的作用相比,APO的作用较弱.本文研究结果证实GnRH和DA能促进斜带石斑鱼脑垂体GH释放和GH mRNA合成.%Gonadotropin-releasing hormone (GnRH) and dopamine (DA) can stimulate growth hormone (GH) release, but their effects on GH mRNA synthesis are controversial and deficient in fish. Orange-spotted grouper (Epinephelus coioides) is a hermaphroditic marine fish with sex reversal. Few data are available concerning the regulation of GH in grouper. In the present study, the effects of GnRH and DA on GH release and GH mRNA expression were determined using pituitary fragments of orange-spotted grouper under static culture conditions. After incubation from 1 h to 24 h, salmon GnRH (sGnRH, 100 nmol/L) stimulated the release of GH and increased the level of GH mRNA time-dependently. The minimum duration of s

  13. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on the body. It stimulates the ...

  14. Cloning and bioinformatics analysis of a fragment cDNA encoding growth hormone-releasing hormone in Tibetan sheep%草地藏系绵羊生长激素释放激素基因部分 cDNA 的克隆及生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    王金玲; 王永; 刘鲁蜀; 陶永平

    2015-01-01

    为了克隆草地藏系绵羊生长激素释放激素基因,采用Trizol法从草地藏系绵羊下丘脑组织中提取总RNA,用反转录-聚合酶链式反应( RT-PCR)进行cDNA扩增并克隆测序,获得长度为207 bp的促生长激素释放激素基因( GHRH)的部分cDNA序列。结果表明获得的草地藏系绵羊GHRH部分cDNA序列与GenBank中注册的绵羊GHRH基因编码起始位置(86位)到292位区域高度同源,仅有1个碱基的差异,该cDNA序列编码69个氨基酸残基,其内含有信号肽序列,该氨基酸序列的31~57位具有典型胰高血糖素类似激素特征的GLUCA结构域。%Total RNA was extracted from the hypothalamus tissues of Tibetan sheep using Trizol method and cDNA was amplified by reverse transcription polymerase chain reaction ( RT-PCR) . The cDNA of Tibetan sheep GHRH gene was cloned from the amplified PCR product and sequenced. The cDNA was 207 bp in length and showed 99% homology with that of com-mon sheep registered in GenBank from the starting position (86) to 292 bp. The cDNA sequence encodes 69 amino acid resi-dues and contains a signal peptide sequence which has a GLUCA domain characterizing glucagon-like hormone at amino acid 31 to 57.

  15. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Peter C. Hindmarsh

    2010-01-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29NH2 bolus (0.5 μg/kg (n=20 or 1.0 μg/kg (n=20, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received 0.5 μg/kg GHRH(1–29NH2 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29NH2 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH (P=.05. Half-life of 20 and 22 K-hGH were not significantly different (P=.55. Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  16. Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released

    Directory of Open Access Journals (Sweden)

    Robinson IainCAF

    2010-05-01

    Full Text Available Background/Aims. 20 Kilodalton-hGH (20 K-hGH is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29 bolus   ( or   (, preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received   GHRH(1–29 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29 doses. Repetitive stimulation reduced the amount of 22 K-hGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH . Half-life of 20 and 22 K-hGH were not significantly different . Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.

  17. Differential involvement of signaling pathways in the regulation of growth hormone release by somatostatin and growth hormone-releasing hormone in orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Wang, Bin; Qin, Chaobin; Zhang, Cong; Jia, Jirong; Sun, Caiyun; Li, Wensheng

    2014-02-15

    Somatostatin is the most effective inhibitor of GH release, and GHRH was recently identified as one of the primary GH-releasing factors in teleosts. In this study, we analyzed the possible intracellular transduction pathways that are involved in the mechanisms induced by SRIF and GHRH to regulate GH release. Using a pharmacological approach, the blockade of the PLC/IP/PKC pathway reversed the SRIF-induced inhibition of GH release but did not affect the GHRH-induced stimulation of GH release. Furthermore, SRIF reduced the GH release induced by two PKC activators. Inhibitors of the AC/cAMP/PKA pathway reversed both the SRIF- and GHRH-induced effects on GH release. Moreover, the GH release evoked by forskolin and 8-Br-cAMP were completely abolished by SRIF. The blockade of the NOS/NO pathway attenuated the GHRH-induced GH release but had minimal effects on the inhibitory actions of SRIF. In addition, inhibitors of the sGC/cGMP pathway did not modify the SRIF- or GHRH-induced regulation of GH release. Taken together, these findings indicate that the SRIF-induced inhibition of GH release is mediated by both the PLC/IP/PKC and the AC/cAMP/PKA pathways and not by the NOS/NO/sGC/cGMP pathway. In contrast, the GHRH-induced stimulation of GH secretion is mediated by both the AC/cAMP/PKA and the NOS/NO pathways and is independent of the sGC/cGMP pathway and the PLC/IP/PKC system.

  18. The Physiology of Growth Hormone-Releasing Hormone (GHRH) in Breast Cancer

    Science.gov (United States)

    2003-06-01

    E., Billestrup, 5813. N., Gonzalez-Manchon, C., and Vale, W. (1992). Endocrino !- 28. Jungwirtb, A., Schally, A. V., Pinski, J., H-almos, G., Groot... Endocrino !. Metab. 82,690-696. Sc!. USA 88, 8749-8753. 33. Barinaga, M., Yamamoto, G., Rivier, C., Vale, W. W., Evans, 10. Berry, S. A., Srivastava, C. H...Matsubara, S., Sato, M., Mizobuchi, M., Niimi, M., and Docherty, K. (1986). J. Endocrino !. 110, 5 1-57. Takahara, J. (1997). Endocrinology 136, 4147-4150

  19. Homologous and heterologous regulation of pituitary receptors for ghrelin and growth hormone-releasing hormone.

    Science.gov (United States)

    Luque, Raúl M; Kineman, Rhonda D; Park, Seungjoon; Peng, Xiao-Ding; Gracia-Navarro, Francisco; Castaño, Justo P; Malagon, María M

    2004-07-01

    Secretion of GH by pituitary somatotropes is primarily stimulated by the hypothalamic GHRH through the activation of a specific G protein-coupled receptor, GHRH receptor (GHRH-R). GH is also released in response to ghrelin, a peptide produced in the stomach, hypothalamus, and pituitary that activates somatotropes via a distinct G protein-coupled receptor, referred to as the GH secretagogue receptor (GHS-R). Here, we have analyzed the expression of both GHRH-R and GHS-R (by multiplex RT-PCR) in porcine pituitary cell cultures, after acute (4 h) treatment with GHRH or ghrelin as well as with other regulators of somatotropes (somatostatin, dexamethasone). Exposure of cultures to GHRH decreased GHRH-R mRNA content and also diminished GHS-R transcript levels. Likewise, ghrelin down-regulated both GHS-R and GHRH-R expression. Interestingly, administration of the activator of adenylate cyclase, forskolin, decreased GHRH-R mRNA levels but had no effect on GHS-R, thus suggesting a distinct contribution of the various intracellular signals operating in somatotropes to the regulation of the expression of these receptors. Accordingly, an atypical activator of adenylate cyclase in the pig somatotrope is low-dose (10(-13) m) somatostatin, which also suppressed GHRH-R mRNA levels without altering GHS-R expression. Finally, dexamethasone did not modify GHRH-R or GHS-R expression. In summary, our data show for the first time that ghrelin, as well as GHRH, mediates homologous and heterologous down-regulation of their own receptor synthesis. However, our results also indicate that the expression of porcine GHRH-R and GHS-R is regulated by distinct signals that may differ from those reported in other mammalian species.

  20. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  1. The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

    Directory of Open Access Journals (Sweden)

    Fernando Cordido

    2010-01-01

    Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R=−0.650, P=.012, HOMA-IR (R=−0.846, P=.001, total cholesterol (R=−0.532, P=.034, and LDL cholesterol (R=−0.692, P=.006 and positively associated with HDL cholesterol (R=0.561, P=.037. These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome.

  2. Role of Sleep and Sleep Loss in Hormonal Release and Metabolism

    OpenAIRE

    Leproult, Rachel; Van Cauter, Eve

    2009-01-01

    Compared to a few decades ago, adults, as well as children, sleep less. Sleeping as little as possible is often seen as an admirable behavior in contemporary society. However, sleep plays a major role in neuroendocrine function and glucose metabolism. Evidence that the curtailment of sleep duration may have adverse health effects has emerged in the past 10 years. Accumulating evidence from both epidemiologic studies and well-controlled laboratory studies indicates that chronic partial sleep l...

  3. Role of sleep and sleep loss in hormonal release and metabolism.

    Science.gov (United States)

    Leproult, Rachel; Van Cauter, Eve

    2010-01-01

    Compared to a few decades ago, adults, as well as children, sleep less. Sleeping as little as possible is often seen as an admirable behavior in contemporary society. However, sleep plays a major role in neuroendocrine function and glucose metabolism. Evidence that the curtailment of sleep duration may have adverse health effects has emerged in the past 10 years. Accumulating evidence from both epidemiologic studies and well-controlled laboratory studies indicates that chronic partial sleep loss may increase the risk of obesity and weight gain. The present chapter reviews epidemiologic studies in adults and children and laboratory studies in young adults indicating that sleep restriction results in metabolic and endocrine alterations, including decreased glucose tolerance, decreased insulin sensitivity, increased evening concentrations of cortisol, increased levels of ghrelin, decreased levels of leptin and increased hunger and appetite. Altogether, the evidence points to a possible role of decreased sleep duration in the current epidemic of obesity. Bedtime extension in short sleepers should be explored as a novel behavioral intervention that may prevent weight gain or facilitate weight loss. Avoiding sleep deprivation may help to prevent the development of obesity, particularly in children.

  4. Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion

    Science.gov (United States)

    Simoes Nunes, C.; Malmlof, K.

    1992-01-01

    Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.

  5. 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...

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

    DEFF Research Database (Denmark)

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

    1987-01-01

    GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal...

  7. Inhibition of Thyroid Hormone Release from Cultured Amphibian Thyroid Glands by Methimazole, 6-Propylthiouracil, and Perchlorate

    Science.gov (United States)

    The research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis. . . This information can then be used to select chemicals for further evaluation in v...

  8. 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

    . 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...... and perpetuate the obese state....

  9. 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...

  10. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  11. 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, ...

  12. Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.

    Science.gov (United States)

    Carter, D A; Saridaki, E; Lightman, S L

    1988-04-01

    The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.

  13. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    Energy Technology Data Exchange (ETDEWEB)

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-03-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

  14. Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Kawa, S; Ueno, T; Iijima, A; Midorikawa, T; Fujimori, Y; Tokoo, M; Oguchi, H; Kiyosawa, K; Imai, Y; Kaneko, G; Kuroda, T; Hashizume, K; Osamura, R Y; Katakami, H

    1997-07-01

    The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

  15. Immunoreactive neuronal pathways of growth hormone-releasing hormone (GRH) in the brain and pituitary of the teleost Gadus morhua.

    Science.gov (United States)

    Pan, J X; Lechan, R M; Lin, H D; Jackson, I M

    1985-01-01

    Using an antiserum directed against the C-terminus of hGRH(1-44)NH2 and another recognizing the mid portion to C-terminal of hGRH(1-40)OH, we identify two immunocytochemically distinct GRH-immunoreactive systems in the brain of the codfish, Gadus morhua. The antiserum directed against GRF(1-44)NH2 stains cell bodies exclusively in the rostral pars distalis. The other antiserum immunoreactive with GRF(1-40)OH reacts with a population of parvocellular and magnocellular neuronal cell bodies in the hypothalamus and with two major axonal pathways which project toward the median eminence and terminate primarily in the pars nervosa. These results indicate the presence of at least two forms of hGRH-like peptides in the teleost which may have different roles in the regulation of pituitary function.

  16. Hormone-refractory prostate cancer and the skeleton

    NARCIS (Netherlands)

    Soerdjbalie-Maikoe, Vidija

    2006-01-01

    Prostate cancer is the second most common cancer in men in the UK. Androgen ablation with luteinising hormone-releasing hormone agonists (LHRH agonists) alone, or in combination with anti-androgens is the standard treatment for men with metastatic prostate cancer. Unfortunately, despite maximal andr

  17. Failure of growth hormone-suppressing agents to affect TSH-releasing hormone- and LH-releasing hormone-induced growth hormone release in acromegaly.

    Science.gov (United States)

    Nakagawa, K; Obara, T

    1977-01-01

    In patients with acromegaly whose basal plasma GH levels were suppressed with 9 mg/day of dexamethasone for 2 days, TRH-(6 cases) and LHRH-(1 case) induced GH release were unaffected when the responses were compared to the basal levels. Phentolamine infusion, 70 mg in 150 min, or hyperglycemia induced by iv infusion of 700 ml of 50% glucose solution also did not suppress TRH-induced GH release in 2 acromegalic patients whose basal GH levels were lowered with these agents alone. These results seem to indicate that dexamethasone does not affect TRH- or LHRH-induced GH release per se, but affects the basal state which determines the absolute level of response. They also support the concept that TRH and LHRH act directly on pituitary tumor cells to release GH in acromegaly.

  18. Diagnóstico clínico e laboratorial da deficiência isolada do hormônio do crescimento em crianças e adolescentes portadores da mutação no gene do receptor do hormônio liberador do hormônio de crescimento em Itabaianinha, Sergipe Clinical and laboratorial diagnosis isolated deficiency of growth hormone in children and adolescents with mutation in receptor gene of growth hormone-releasing hormone in Itabaianinha, SE, Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Menezes

    2004-12-01

    central adiposity. CONCLUSION: The results showed that the IDGH patients from Itabaininha presented a growth hormone isolated Type IB deficiency. In addition, the lower height was not associated with pituitary alterations or other non-hormone pathologies.

  19. Effect of dietary macronutrients on postprandial incretin hormone release and satiety in obese and normal-weight women.

    Science.gov (United States)

    Wikarek, Tomasz; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena

    2014-01-28

    The aim of the present study was to assess the effect of dietary macronutrients on postprandial incretin responses and satiety and hunger sensation in obese and normal-weight women. A total of eleven obese and nine normal-weight women were recruited for the assessment of plasma concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and insulin and the sensation of satiety and hunger using a visual analogue scale before and during a 6 h period after administration of three different macronutrient test meals. The AUCtotal GLP-1 and AUCtotal GIP values were decreased in obese women after the consumption of a fatty meal and all the test meals, respectively. However, the AUCtotal insulin value after a carbohydrate meal was greater in the obese group. The AUCtotal satiety value was decreased only after the intake of the protein meal in obese women when compared with normal-weight women. After the consumption of the fatty meal, a significant positive correlation between maximum satiety sensation and the AUCtotal GLP-1 value in the obese group and that between minimum hunger sensation and the AUCtotal GLP-1 value in the normal-weight group were observed. In conclusion, the findings of the present study suggest that: (1) satiety sensation after consumption of carbohydrate and protein meals in the obese group is related to the postprandial insulin response, while after consumption of a fatty meal, it is related to the postprandial GLP-1 release; (2) the postprandial GIP response does not influence the sensation of satiety and hunger; (3) the reduced GLP-1 release after the intake of a fatty meal in obese individuals may explain impaired satiety sensation; (4) the impaired postprandial GIP response is not related to the consumption of macronutrients and may be the early indicator of incretin axis dysfunction in obese women.

  20. Effects of guar gum and cellulose on glucose absorption, hormonal release and hepatic metabolism in the pig

    Science.gov (United States)

    Nunes, C. S.; Malmlof, K.

    1992-01-01

    Six Large White pigs (mean body-weight 59 (SE 1.7) kg) were surgically fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein, as well as with electromagnetic flow probes around the portal vein and the hepatic artery, and allowed to recover. The non-anaesthetized animals were given a basal non-fibre diet (diet A) alone or together with 60 g guar gum/kg (diet B) or 150 g purified cellulose/kg (diet C) by substitution for mica. The diets were given for weekly periods and according to a replicated 3 x 3 Latin square design. On the last day of each such adaptation period, test meals of 800 g were given before blood sampling. Sampling was continued for 8 h. Guar gum strongly reduced glucose apparent absorption without changing the absorption and the hepatic uptake profiles. Production rates of insulin, gastric inhibitory polypeptide and insulin-like growth factor-1 (IGF-1) were lowest after guar gum ingestion. However, the reductions in peripheral blood insulin levels caused by guar gum were not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly secreted by the gut, whereas the liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut-produced IGF-1. Guar gum ingestion appeared also to decrease glucagon secretion. Cellulose at the level consumed had very few effects on the variables considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the metabolic effects described.

  1. 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

    -1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P

  2. ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release

    OpenAIRE

    Bernardi, H; de Weille, J.R.; Epelbaum, J; Mourre, C; Amoroso, S.; Slama, A; Fosset, M; Lazdunski, M

    1993-01-01

    The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by an...

  3. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor.

    Science.gov (United States)

    Asa, S L; Scheithauer, B W; Bilbao, J M; Horvath, E; Ryan, N; Kovacs, K; Randall, R V; Laws, E R; Singer, W; Linfoot, J A

    1984-05-01

    We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.

  4. Acromegaly caused by a growth hormonereleasing hormone secreting carcinoid tumour of the lung : the effect of octreotide treatment

    NARCIS (Netherlands)

    De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.

    2007-01-01

    in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the

  5. Acromegaly caused by a growth hormonereleasing hormone secreting carcinoid tumour of the lung : the effect of octreotide treatment

    NARCIS (Netherlands)

    De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.

    2007-01-01

    in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the lun

  6. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    Science.gov (United States)

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  7. Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine.

    Science.gov (United States)

    Rigamonti, A E; Marazzi, N; Cella, S G; Cattaneo, L; Müller, E E

    1998-02-01

    Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0.9% saline (5 ml/h), somatostatin (SS, 4 or 8 micrograms/kg/h), or pretreatment with pirenzepine (PZ, 0.6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 micrograms/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 micrograms/kg i.v.) or GHRH plus HEXA. In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting. The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions. In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs. These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA. It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

  8. Peak Growth Hormone-Releasing Hormone-Arginine-Stimulated Growth Hormone Is Inversely Associated with Intramyocellular and Intrahepatic Lipid Content in Premenopausal Women with Obesity

    OpenAIRE

    Bredella, Miriam A.; Torriani, Martin; Thomas, Bijoy J.; Ghomi, Reza Hosseini; Brick, Danielle J.; Gerweck, Anu V.; Miller, Karen K

    2009-01-01

    Context: Visceral adiposity is a strong determinant of GH secretion, and low endogenous GH secretion is associated with increased insulin resistance, a key component of the metabolic syndrome. Increased fat accumulation in skeletal muscle and liver may play an etiological role in the development of insulin resistance and other complications of the metabolic syndrome. Little is known about the role of decreased endogenous GH secretion in the pathogenesis of insulin resistance in obesity.

  9. Clinical characteristics and outcome of acromegaly induced by ectopic secretion of growth hormone-releasing hormone (GHRH): a French nationwide series of 21 cases.

    Science.gov (United States)

    Garby, Laetitia; Caron, Philippe; Claustrat, Francine; Chanson, Philippe; Tabarin, Antoine; Rohmer, Vincent; Arnault, Gwenaëlle; Bonnet, Fabrice; Chabre, Olivier; Christin-Maitre, Sophie; du-Boullay, Hélène; Murat, Arnaud; Nakib, Ihab; Sadoul, Jean-Louis; Sassolas, Geneviève; Claustrat, Bruno; Raverot, Gérald; Borson-Chazot, Françoise

    2012-06-01

    Ectopic GHRH secretion is a rare cause of acromegaly, and case reports are mainly isolated. From the registry of the sole laboratory performing plasma GHRH assays in France, we identified cases of ectopic GHRH secretion presenting with acromegaly between 1983 and 2008. Twenty-one patients aged 14-77 yr were identified from 12 French hospitals. Median GHRH was 548 (270-9779) ng/liter. Outcome measures included description of tumor features and outcome and the relation between plasma GHRH values and tumor site, size, and spread. The primary neuroendocrine tumor was identified for 20 of 21 patients (12 pancreatic, seven bronchial, one appendicular). Tumors were large (10-80 mm), identified on computed tomography scan in 18 cases and by endoscopic ultrasound and somatostatin receptor scintigraphy in two. Somatostatin receptor scintigraphy had a similar sensitivity to computed tomography scan (81 vs. 86%). Tumors were all well differentiated; 47.6% had metastasized at the time of diagnosis of acromegaly. After a median follow-up of 5 yr, 85% of patients were alive. Ninety-one percent of patients whose tumor was completely removed were considered in remission, and most had normalized plasma GHRH. The remaining patients were treated with somatostatin analogs: IGF-I normalized except for one patient who required pegvisomant, but GHRH levels remained elevated. No correlations were found between GHRH levels and tumor site or size or the existence of metastases. Identification of increased plasma GHRH during follow-up was an accurate indicator of recurrence. The prognosis of endocrine tumors responsible for GHRH secretion appears relatively good. Plasma GHRH assay is an accurate tool for diagnosis and follow-up.

  10. 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

    hazards regression model and a conditional logistic regression model was used for a case-control analysis of odds ratios (ORs). RESULTS: Patients received degarelix monotherapy (n = 972) or LHRH agonist (n = 483) of whom 57 also received AA. Overall, prostate-specific antigen progression-free survival....../ml in the LHRH agonist + AA group, a case-control analysis using a conditional logistic regression model was utilized. This resulted in an OR for PSA PFS of 0.42 (95% CI 0.20-0.89; p = 0.023) in the overall population, and 0.35 (95% CI 0.13-0.96; p = 0.042) in patients with PSA >50 ng/ml at baseline, when...... protection therapy in patients with prostate cancer when a case-control analysis was used to compensate for differences between treatment groups....

  11. Hormonal contraception for human males: prospects

    Institute of Scientific and Technical Information of China (English)

    P.R.K.Reddy

    2000-01-01

    Development of an ideal hormonal contraceptive for man has been the goal of several research workers during the past few decades. Suppression of pituitary gonadotropic hormones, which in turn would inhibit spermatogenesis while maintaining normal libido and potentia has been the approach for a contraceptive agent. Intramuscularly administered and orally active testosterone or testosterone in combination with progesterone have been shown to cause inhibition of spermatogenesis resulting in azoospermia in normal men. Similarly testosterone has been used in combination with gonadotropin releasing hormone antagonists and agonists to inhibit pituitary gonadotropic hormone release. Immunological approach to neutralize the circulating levels of follicle stimulating hormone has also been shown to cause inhibition of spermatogenesis. The available literature shows that testosterone causes reversible azoospermia without any significant side effects in Asian population effectively and appears to be a promising chemical for control of fertility in man.( Asian J Androl 2000 ; 2 : 46 - 50 )

  12. Growth hormone secretagogues: out of competition.

    Science.gov (United States)

    Pinyot, Armand; Nikolovski, Zoran; Bosch, Jaume; Such-Sanmartín, Gerard; Kageyama, Shinji; Segura, Jordi; Gutiérrez-Gallego, Ricardo

    2012-01-01

    Growth hormone secretagogues (GHS) constitute a new GH deficiency treatment increasing exponentially in number and improved potency and bioavailability over the last decade. The growth hormone releasing activity makes these compounds attractive for the artificial improvement of the human sports skills, now that recombinant human growth hormone (rhGH) administration is effectively detected. The GHS family is extremely diverse both in number and chemical heterogeneity and keeps growing continuously. In this paper, a general screening test is proposed. To develop a universal method, the single common property of growth hormone secretagogues has been targeted: their capacity to bind to the GHS receptor 1a (GHS-R1a). Pretreated urine samples have been tested in a competition assay where eventually the GHS presence detached a radiolabelled ligand from the receptor in a dose-dependent manner. Blank urine samples were processed to determine potential age, gender and exercise effects, and to define a threshold beyond which a specimen is considered positive. Samples from a growth hormone releasing peptide 2 (GHRP-2) excretion study corroborated the screening assay applicability with a detection window of approximately 4.5 h, and results were confirmed by comparison with a dedicated LC-MS quantification of the intact compound.

  13. Thyroid hormone and the heart.

    Science.gov (United States)

    Moolman, J A

    2002-01-01

    Thyroid hormone has important cardiovascular effects, and abnormalities of its production cause cardiovascular morbidity. The role of both excessive and insufficient thyroid hormone production in the pathogenesis of clinical cardiac diseases can be deduced from thyroid hormone-induced molecular changes. Thyroid hormone regulates the expression of myocardial genes regulating the handling of calcium, which affects both systolic and diastolic myocardial function. Thyroid hormone also has indirect and direct effects on peripheral vascular smooth muscle tone, and alters the coupling of the left ventricle and arterial system. Excessive production of thyroid hormone results in an increased cardiac output as well as increased cardiac work efficiency, but reduced cardiac reserve. Amiodarone therapy for cardiac rhythm can cause both hyper- and hypothyroidism. Amiodarone-induced thyrotoxicosis (AIT) can be due to either excessive thyroid hormone production (type I AIT) or thyroid hormone release due to an inflammatory condition (type II AIT). Classification of AIT is helpful in guiding therapy. Amiodarone causes changes in the thyroid function tests of euthyroid patients on therapy--it inhibits the conversion of T(4) and T(3), which results in decreased T(3) and slightly increased T(4) serum levels in euthyroid patients. Baseline thyroid functions should therefore be determined before starting amiodarone therapy, and at 6-monthly intervals thereafter.

  14. Hormonal cytoreduction and radiotherapy for carcinoma of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Shearer, R.J.; Davies, J.H.; Gelister, J.S.K.; Dearnaley, D.P. (Royal Marsden Hospital, London (United Kingdom))

    1992-05-01

    We report the effect on prostatic volume of the administration of the luteinising hormone-releasing hormone (LHRH) analogue goserelin in 22 patients with locally advanced carcinoma of the prostrate; 20 achieved a significant reduction in volume, the median volume being 66 ml before treatment and 30 ml after 17 weeks. If used before external beam radiotherapy (RT), volume reduction will permit smaller boost fields and thus potentially reduce adverse radiotherapy effects. In addition, reducing tumour volume before RT may lead to an increase in local control. We discuss the possible role of hormonal volume reduction in the management of prostatic cancer. (Author).

  15. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    OpenAIRE

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K.

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. Th...

  16. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Coakley, J H; Moorcraft, J; Hipkin, L J; Smith, C S; Griffiths, R D; Edwards, R H

    1988-12-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  17. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

    OpenAIRE

    Coakley, J. H.; Moorcraft, J; Hipkin, L J; Smith, C. S.; R.D. Griffiths; Edwards, R H

    1988-01-01

    Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

  18. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    Energy Technology Data Exchange (ETDEWEB)

    Menon, M.; Peegel, H.; Katta, V.

    1985-02-15

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction.

  19. Steroid hormones and sleep regulation.

    Science.gov (United States)

    Terán-Pérez, G; Arana-Lechuga, Y; Esqueda-León, E; Santana-Miranda, R; Rojas-Zamorano, J Á; Velázquez Moctezuma, J

    2012-10-01

    In the search of the sleep substance, many studies have been addressed for different hormones, responsible for sleep-wake cycle regulation. In this article we mentioned the participation of steroid hormones, besides its role regulating sexual behavior, they influence importantly in the sleep process. One of the clearest relationships are that estrogen and progesterone have, that causing changes in sleep patterns associated with the hormonal cycles of women throughout life, from puberty to menopause and specific periods such as pregnancy and the menstrual cycle, including being responsible for some sleep disorders such as hypersomnia and insomnia. Another studied hormone is cortisol, a hormone released in stressful situations, when an individual must react to an extraordinary demand that threatens their survival, but also known as the hormone of awakening because the release peak occurs in the morning, although this may be altered in some sleep disorders like insomnia and mood disorders. Furthermore neurosteroids such as pregnanolone, allopregnanolone and pregnenolone are involved in the generation of slow wave sleep, the effect has been demonstrated in experimental animal studies. Thus we see that the sleep and the endocrine system saved a bidirectional relationship in which depends on each other to regulate different physiological processes including sleep.

  20. Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations.

    Science.gov (United States)

    Chanson, Philippe; Cailleux-Bounacer, Anne; Kuhn, Jean-Marc; Weryha, Georges; Chabre, Olivier; Borson-Chazot, Françoise; Dubois, Séverine; Vincent-Dejean, Caroline; Brue, Thierry; Fedou, Christine; Bresson, Jean-Louis; Demolis, Pierre; Souberbielle, Jean-Claude

    2010-08-01

    The GHRH plus arginine (GHRH+Arg) test is a promising alternative to the insulin tolerance test (ITT) for diagnosis of adult GH deficiency (AGHD). The objectives of the study were to validate the GHRH+Arg test for diagnosis of AGHD, using the ITT as comparator and a GH assay calibrated according to recent international recommendations, and to study the repeatability and tolerance of both tests. This was a multicenter, randomized, open-label, phase III study. The study was conducted at 10 French university hospitals. Sixty-nine subjects (38 and 15 with high and low probability of GH deficiency, respectively, and 16 healthy controls) were randomized: 35 to the GHRH+Arg-GHRH+Arg-ITT test sequence and 34 to the ITT-ITT-GHRH+Arg test sequence. Each subject underwent three tests of GH secretion separated by 24 h or more. The primary variable used for response assessments was serum peak GH response. Test results were compared with the final AGHD diagnosis. Peak GH responses in the two tests were strongly correlated. A cutoff value of 7.89 microg/liter for GHRH+Arg corresponding to 3 microg/liter for ITT was calculated. The cutoff value leading to 95% specificity with the GHRH+Arg test was measured at about 3.67 microg/liter (sensitivity 79.0%). Intermethod agreement and repeatability were high. Both tests were well tolerated. A preference for the GHRH+Arg test was expressed by 74% of subjects. The GHRH+Arg test demonstrated good accuracy and repeatability, was at least as sensitive as the ITT, and was associated with better subject acceptability. The GHRH+Arg test represents a good alternative to the ITT for the diagnosis of AGHD.

  1. Aluminum, parathyroid hormone, and osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

    1983-01-01

    Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

  2. Evidence for a functional link between the heme oxygenase-carbon monoxide pathway and corticotropin-releasing hormone release from primary cultures of human trophoblast cells.

    Science.gov (United States)

    Navarra, P; Miceli, F; Tringali, G; Minici, F; Pardo, M G; Lanzone, A; Mancuso, S; Apa, R

    2001-01-01

    The gene expression and synthesis of both constitutive and inducible heme oxygenase (HO) isoforms have been recently described in human placental cells, but the functional role(s) of this biochemical pathway in placental physiology and pathology is still unclear. In the present study, we have investigated whether HO activity is involved in the control of CRH secretion from trophoblast cells. Fluctuations in HO activity were induced in primary cultures of human trophoblast cells using well-known activators and inhibitors of HO, and the subsequent changes in CRH secretion were monitored measuring CRH immunoreactivity released into the incubation medium. It was found that the increase in HO activity induced by hemin or cobalt chloride (CoCl(2)) was associated with parallel significant increases in CRH release. This effect was probably caused by the gaseous HO end-product, carbon monoxide (CO), because it was blocked by the HO inhibitor tin-mesoporphyrin-9, but it was not mimicked by stable HO end-products, biliverdin and bilirubin. We have also investigated whether stimulation of CRH release induced by HO was mediated by the cyclooxygenase (COX) pathway. Indeed, hemin also caused significant increases in PGE2 release in this experimental paradigm. However, CoCl(2), which also enhances CRH release, had no stimulatory effect and actually inhibited PG secretion; moreover, a nonselective COX inhibitor, indomethacin, failed to counteract hemininduced CRH release. Taken collectively, these findings suggested that modulation of CRH secretion by the HO-CO system occurs through a mechanism independent of COX activity.

  3. Growth Hormone-Releasing Peptide-2 Suppresses Vascular Oxidative Stress in ApoE−/− Mice But Does Not Reduce Atherosclerosis

    OpenAIRE

    2009-01-01

    GH-releasing peptide-2 (GHRP-2) is a synthetic peptide that increases circulating GH and IGF-I levels. It also binds to CD36, a scavenger receptor for oxidized low-density lipoprotein (OxLDL), and may prevent cellular uptake of this proatherogenic complex. To determine its potential antiatherogenic effects, GHRP-2 (20 μg twice daily) was administered sc to ApoE−/− mice for 12 wk. GHRP-2 increased circulating IGF-I 1.2- to 1.6-fold and decreased circulating interferon-γ by 66%. Although GHRP-2...

  4. The positive effects of growth hormone-releasing peptide-6 on weight gain and fat mass accrual depend on the insulin/glucose status.

    Science.gov (United States)

    Granado, Miriam; García-Cáceres, Cristina; Frago, Laura M; Argente, Jesús; Chowen, Julie A

    2010-05-01

    Ghrelin and GH secretagogues, including GH-releasing peptide (GHRP)-6, stimulate food intake and adiposity. Because insulin modulates the hypothalamic response to GH secretagogues and acts synergistically with ghrelin on lipogenesis in vitro, we analyzed whether insulin plays a role in the metabolic effects of GHRP-6 in vivo. Streptozotocin-induced diabetic rats received saline, GHRP-6, insulin, or insulin plus GHRP-6 once daily for 8 wk. Rats receiving saline suffered hyperglycemia, hyperphagia, polydipsia, and weight loss. Insulin, but not GHRP-6, improved these parameters (P insulin an increase. Diabetic rats receiving insulin plus GHRP-6 gained more weight and had increased epididymal fat mass and serum leptin levels compared with all other groups (P Insulin normalized these parameters to control values. GHRP-6 treatment increased FAS and glucose transporter-4 gene expression and potentiated insulin's effect on epididymal fat mass, adipocyte size (P insulin exert an additive effect on weight gain and visceral fat mass accrual in diabetic rats, indicating that some of GHRP-6's metabolic effects depend on the insulin/glucose status.

  5. 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...... profiles, the decreased GH responses to insulin-induced hypoglycemia and L-arginine, the decreased basal IGF-I levels and IGF-I/IGFBP-3 molar ratio, as well as the elevated insulin levels were returned to normal after a massive weight loss in the obese subjects. In conclusion, the present study has shown...... 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...

  6. Influence of catecholamines, prostaglandins and thyroid hormones on growth hormone secretion by chicken pituitary cells in vitro.

    Science.gov (United States)

    Donoghue, D J; Perez, F M; Diamante, B S; Malamed, S; Scanes, C G

    1990-01-01

    In young chickens plasma concentrations of growth hormone (GH) are depressed by prostaglandins (PG) E1 and E2, epinephrine, norepinephrine, alpha 2 and beta agonists or thyroid hormones. A primary culture of chicken adenohypophyseal cells was used to examine the direct effects of these agents at the level of the pituitary as evaluated by GH release in the presence and absence of growth hormone releasing factor (GRF). Following collagenase dispersion and culture (preincubation, 48 hr) cells were exposed (incubation, 2 hr) to test agents, except for thyroid hormones which were added during the preincubation, and incubation period. Growth hormone release was increased (P less than .05) in the presence of PGE1 (10(-8)M by 34%; 10(-7)M by 54%), PGE2 (10(-8)M by 29%; 10(-7)M by 29%), PGF2 alpha (10(-8)M by 28%), and the beta agonist isoproterenol (10(-7)M by 46%). Basal GH release from chicken pituitary cells was not affected by dopamine, norepinephrine, epinephrine, thyroxine (T4), triiodothyronine (T3), or alpha adrenergic agonists. Growth hormone releasing factor stimulated GH release was not affected by the presence of prostaglandins E1, E2 or F2 alpha in the incubation media. However, GRF stimulated GH release was reduced by high doses of catecholamines: dopamine (10(-6)M by 34%), norepinephrine (10(-6)M by 74%), epinephrine (10(-8)M by 47%; 10(-7)M by 41%; 10(-6)M by 89%), and by the alpha 1 adrenergic agonist, phenylephrine (10(-7)M by 52%), the alpha 2 agonist, clonidine (10(-8)M by 34%; 10(-7)M by 83%) and the beta agonist, isoproterenol (10(-7)M by 64%).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Chitosan-Nanoconjugated Hormone Nanoparticles for Sustained Surge of Gonadotropins and Enhanced Reproductive Output in Female Fish

    OpenAIRE

    Mohd Ashraf Rather; Rupam Sharma; Subodh Gupta; S Ferosekhan; V L Ramya; Jadhao, Sanjay B.

    2013-01-01

    A controlled release delivery system helps to overcome the problem of short life of the leutinizing hormone releasing hormone (LHRH) in blood and avoids use of multiple injections to enhance reproductive efficacy. Chitosan- and chitosan-gold nanoconjugates of salmon LHRH of desired size, dispersity and zeta potential were synthesized and evaluated at half the dose rate against full dose of bare LHRH for their reproductive efficacy in the female fish, Cyprinus carpio. Whereas injections of bot...

  8. Effects of oleic acid and olive oil on gastric emptying, gut hormone secretion and appetite in lean and overweight or obese males

    DEFF Research Database (Denmark)

    Damgaard, Morten; Graff, Jesper; Fuglsang, Stefan

    2013-01-01

    lean subjects, free fatty acid (FFA) promotes gut hormone release, delays gastric emptying, and reduces appetite and energy intake more than an isocaloric load of triglyceride (TG). In obesity, the gastrointestinal sensitivity to lipids may be reduced. Therefore, we compared the effects of the FF...... oleic acid and the TG olive oil on gut hormone secretion, gastric emptying, appetite, and energy intake in lean and overweight/obese subjects....

  9. Hormonal modulation of endothelial NO production.

    Science.gov (United States)

    Duckles, Sue P; Miller, Virginia M

    2010-05-01

    Since the discovery of endothelium-derived relaxing factor and the subsequent identification of nitric oxide (NO) as the primary mediator of endothelium-dependent relaxations, research has focused on chemical and physical stimuli that modulate NO levels. Hormones represent a class of soluble, widely circulating chemical factors that impact production of NO both by rapid effects on the activity of endothelial nitric oxide synthase (eNOS) through phosphorylation of the enzyme and longer term modulation through changes in amount of eNOS protein. Hormones that increase NO production including estrogen, progesterone, insulin, and growth hormone do so through both of these common mechanisms. In contrast, some hormones, including glucocorticoids, progesterone, and prolactin, decrease NO bioavailability. Mechanisms involved include binding to repressor response elements on the eNOS gene, competing for co-regulators common to hormones with positive genomic actions, regulating eNOS co-factors, decreasing substrate for eNOS, and increasing production of oxygen-derived free radicals. Feedback regulation by the hormones themselves as well as the ability of NO to regulate hormonal release provides a second level of complexity that can also contribute to changes in NO levels. These effects on eNOS and changes in NO production may contribute to variability in risk factors, presentation of and treatment for cardiovascular disease associated with aging, pregnancy, stress, and metabolic disorders in men and women.

  10. Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

    Science.gov (United States)

    Fine, R N

    1991-04-01

    Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.

  11. Chitosan-nanoconjugated hormone nanoparticles for sustained surge of gonadotropins and enhanced reproductive output in female fish.

    Science.gov (United States)

    Rather, Mohd Ashraf; Sharma, Rupam; Gupta, Subodh; Ferosekhan, S; Ramya, V L; Jadhao, Sanjay B

    2013-01-01

    A controlled release delivery system helps to overcome the problem of short life of the leutinizing hormone releasing hormone (LHRH) in blood and avoids use of multiple injections to enhance reproductive efficacy. Chitosan- and chitosan-gold nanoconjugates of salmon LHRH of desired size, dispersity and zeta potential were synthesized and evaluated at half the dose rate against full dose of bare LHRH for their reproductive efficacy in the female fish, Cyprinus carpio. Whereas injections of both the nanoconjugates induced controlled and sustained surge of the hormones with peak (Phormone in fish.

  12. Levels of hormones and cytokines associated with growth in Honamlı and native hair goats.

    Science.gov (United States)

    Devrim, A K; Elmaz, O; Mamak, N; Sudagidan, M

    2015-01-01

    This study was designed to assess alterations of hormone and cytokine levels associated with growth period during puberty in Honamlı goats which were identified as a new goat breed and had one of the highest meat production potential among the other goat breeds in Turkey. Honamlı goats are originated from native hair goats, so parallel studies of sampling and analyzing were conducted also in native hair goats which have moderate meat production. Blood serum samples of Honamlı (n=90) and native hair goats (n=90) were obtained from the pure herds in Korkuteli and Ka districts of Anatolia. Concentrations of growth hormone (GH), myostatin (MSTN), insulin-like growth factor (IGF), growth hormone releasing hormone (GHRH), growth hormone releasing peptide (GHRP), leptin, transforming growth factor-betal (TGF-β1) and vascular endothelial cell growth factor (VEGF) levels were measured by ELISA in each breed in the age groups of 4, 8 and 12 months. The present results indicate interesting correlations among the age groups and all the examined hormone and cytokine parameters exhibited significant (Phormonal alterations of goats could occur at 4th month of age. The results reported here emphasize the primary role played by GH, MSTN, IGF-1, leptin, GHRH, GHRP, TGF-βi and VEGF in the first year growth period of goats.

  13. The effects of hypokalaemia on the hormone exocytosis in adenohypophysis and prolactinoma cell culture model systems.

    Science.gov (United States)

    Molnár, Z; Pálföldi, R; László, A; Radács, M; László, M; Hausinger, P; Tiszlavicz, L; Rázga, Z; Valkusz, Z; Gálfi, M

    2014-11-01

    The extracellular ion milieu determines the exocytosis mechanism that is coupled to spontaneous electrical activity. The K(+) ion plays crucial role in this mechanism: as the potassium current is associated with membrane hyperpolarization and hormone release through protein cascade activation. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular K(+) levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.In our experimental study, female Wistar rats (n=20) were treated with estrone-acetate (150 μg/kg b.w./week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used to assess the apoptotic cells.Differences between the effects of hypokalaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (pprolactinoma cell cultures compared to untreated groups. Immunocyto-chemistry showed that Bcl-2 expression was reduced under hypokalaemic conditions.The decrease in hormone exocytosis was tightly correlated to the extracellular K(+) in both cell types, leading to the conclusion that external K(+) may be the major factor for the inhibition of hormone release. The significant increase in hormone content in supernatant media suggests that hypokalaemia may play important role in apoptosis.

  14. Meal induced gut hormone secretion is altered in aerobically trained compared to sedentary young healthy males

    DEFF Research Database (Denmark)

    Lund, Michael Taulo; Taudorf, Lærke; Hartmann, Bolette

    2013-01-01

    was to assess and compare gut hormone response and satiety changes after a liquid meal intake in young, healthy T and UT males. Postprandial gut hormone release and subjective feelings of hunger, satiety, fullness and prospective food consumption were assessed before and frequently for the following 3 h after...... concentration was higher in T versus UT, but the response in the following 3 h after a liquid meal was similar in T and UT. Satiety measures did not differ between groups throughout the test. It is possible that in aerobically T subjects, a lower GIP release is partly responsible for a lower postprandial...

  15. Pancreatic hormones are expressed on the surfaces of human and rat islet cells through exocytotic sites

    DEFF Research Database (Denmark)

    Larsson, L I; Hutton, J C; Madsen, O D

    1989-01-01

    . Electron microscopy reveals the labeling to occur at sites of exocytotic granule release, involving the surfaces of extruded granule cores. The surfaces of islet cells were labeled both by polyclonal and monoclonal antibodies, excluding that receptor-interacting, anti-idiotypic hormone antibodies were...... responsible for the staining. Human insulin cells were surface-labeled by monoclonal antibodies recognizing the mature secretory products, insulin and C-peptide but not with monoclonal antibodies specific for proinsulin. Thus, routing of unprocessed preproinsulin to the cell surface may not account...... for these results. It is concluded that the staining reflects interactions between the appropriate antibodies and exocytotic sites of hormone release....

  16. Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix.

    Science.gov (United States)

    Barkin, Jack; Burton, Shelley; Lambert, Carole

    2016-02-01

    The gonadotropin-releasing hormone (GnRH) receptor antagonist degarelix has several unique characteristics compared to luteinizing hormone-releasing hormone (LHRH) analogs used in the management of prostate cancer. Notable differences of GnRH receptor antagonists include no flare reaction, and a more rapid suppression of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate-specific antigen (PSA) compared to LHRH analogs. Despite emerging evidence supporting the use of GnRH receptor antagonists over the more widely used LHRH analogs in the management of prostate cancer, physicians may be reluctant to prescribe degarelix. They may be concerned about patient complaints about injection-site reactions (ISRs). The subcutaneous injection of degarelix has been associated with a higher rate of ISRs compared with the intramuscular injections of LHRH analogs. This "How I Do It" article describes techniques and strategies that have been developed by physicians and nurses to reduce the discomfort associated with the subcutaneous delivery of degarelix.

  17. Activation of GABA B receptors in the anterior pituitary inhibits prolactin and luteinizing hormone secretion.

    Science.gov (United States)

    Lux-Lantos, V; Rey, E; Libertun, C

    1992-11-01

    Previous work from our laboratory showed that baclofen could lower serum prolactin (PRL) levels acting at the central nervous system. The present experiments were designed to evaluate whether the gamma-aminobutyric acid B agonist was also effective in inhibiting hormone release at the pituitary level. In monolayer cultures of adenohypophyseal dispersed cells, baclofen inhibited basal PRL secretion after 1 or 2 h of incubation. This inhibition was significantly abolished by three antagonists: phaclofen, 3-aminopropyl-phosphonic acid and 4-aminobutylphosphonic acid. Furthermore, baclofen inhibited the thyrotropin-releasing hormone-induced PRL release in a concentration-dependent manner. With regard to gonadotropin secretion, baclofen was unable to modify basal luteinizing hormone (LH) secretion, but significantly inhibited the LH-releasing hormone-induced LH release. These results show that baclofen, in addition to its central neuroendocrine effects, inhibits pituitary hormone secretion, under basal and/or stimulated conditions, by direct action at the pituitary level.

  18. Immunoaffinity purification of peptide hormones prior to liquid chromatography-mass spectrometry in doping controls.

    Science.gov (United States)

    Thomas, Andreas; Schänzer, Wilhelm; Delahaut, Philippe; Thevis, Mario

    2012-02-01

    For most peptide hormones prohibited in elite sports the concentrations in plasma or urine are very low (pg/mL). Accordingly, hyphenated purification and enrichment steps prior to mass spectrometric detection are required to obtain sufficient doping control assays. Immunoaffinity purification in combination with nano-scale liquid chromatography coupled to high resolution/high accuracy mass spectrometry was found to have the potential of providing the necessary sensitivity and unambiguous specificity to produce reliable results. With the presented methodology 12 prohibited peptides (porcine insulin, Novolog, Apidra, Lantus DesB30-32 metabolite, Humalog and human insulin, Synacthen (synthetic ACTH analogue), luteinizing hormone-releasing hormone (LH-RH), growth hormone releasing hormone (GH-RH(1-29)) and CJC-1295 (GH-RH analogue), LongR(3)-IGF-1 and IFG-1) were simultaneously purified from plasma/serum or urine. With limits of detection for each target compound ranging in the low pg/mL level (urine), the method enables the determination of urinary peptides at physiologically relevant concentrations. For each class of peptides an appropriate antibody and a respective internal standard was implemented ensuring robust analysis conditions. Due to the fast and simple sample preparation procedure (∼25 samples per day) and the fact that all materials are commercial available, the implementation of the methodology to laboratories from other analytical fields (forensics, pharmacokinetic sciences, etc.) is enabled.

  19. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  20. Detection of catecholamine and luteinizing hormone-releasing hormone (LH-RH) containing nerve endings in the median eminence and the organon vasculosum laminae terminalis by fluorescence histochemistry and immunohistochemistry on the same microscopic sections.

    Science.gov (United States)

    Ibata, Y; Watanabe, K; Kinoshita, H; Kubo, S; Sano, Y; Sin, S; Hashimura, E; Imagawa, K

    1979-02-01

    Distribution of catecholamine (CA) and LH-RH nerve endings in the median eminence (ME) and the organon vasculosum laminae terminalis (OVLT) of the rat was investigated by application of fluorescence histochemistry and immunohistochemistry on the same sections of the tissue. In the ME, those two kinds of endings coexisted in the lateral portion of the middle part of ME, and in the wall of tuberoinfundibular sulcus, where they might be considered to have functional correlation. In the OVLT they were also distributed in fairly near distance, but they were not so closely associated as observed in the ME.

  1. Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

    Institute of Scientific and Technical Information of China (English)

    Haogang Xue; Chunying Yang; Xiaodong Ge; Weiqi Sun; Chun Li; Mingyu Qi

    2013-01-01

    Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kisspeptin antagonist peptide 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

  2. Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus)

    OpenAIRE

    Illing, Nicola; Troskie, Brigitte E.; Nahorniak, Carol S.; Janet P Hapgood; Peter, Richard E.; Millar, Robert P.

    1999-01-01

    In the goldfish (Carassius auratus) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His5,Trp7,Tyr8]GnRH) and salmon GnRH ([Trp7,Leu8]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring...

  3. Growth Hormone

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Growth Hormone Share this page: Was this page helpful? Also known as: GH; Human Growth Hormone; HGH; Somatotropin; Growth Hormone Stimulation Test; Growth ...

  4. Hormonal changes during puberty and their relationship to fat distribution.

    Science.gov (United States)

    Roemmich, James N.; Rogol, Alan D.

    1999-01-01

    In adults, abdominal visceral adiposity is related to an increased risk of cardiovascular diseases, Type 2 diabetes mellitus, and stroke. The antecedents of these conditions likely begin with the alterations in body fat distribution during childhood and adolescence. The sexually dimorphic alterations in fat distribution are influenced by sex differences in hormone concentrations, anatomical differences in the number and density of specific hormone receptors, capillary blood flow, and the activity of enzymes promoting lipid synthesis or degradation. Hormones influencing the amount and regional distribution of adipose tissue during puberty include cortisol, insulin, growth hormone, and the sex steroids. Cortisol and insulin promote fat deposition while the sex steroids and GH stimulate lipolysis. An overly sensitive hypothalamic-pituitary-adrenal axis may exist in obesity and disrupt the balance between the lipogenic effects of cortisol and insulin and the lipolytic effects of sex steroids and growth hormone. Leptin is released from the adipocytes and may act as a metabolic signal to the hypothalamic areas controlling satiety, energy expenditure, and the regulation of cortisol, insulin, sex steroid and growth hormone release. The complex issues of the hormonal control of alterations in body fat distribution during puberty are developed and a working model is proposed. Am. J. Hum. Biol. 11:209-224, 1999. Copyright 1999 Wiley-Liss, Inc.

  5. Growth hormone (GH-releasing hormone and GH secretagogues in normal aging: Fountain of Youth or Pool of Tantalus?

    Directory of Open Access Journals (Sweden)

    Elizabeth C Hersch

    2008-03-01

    Full Text Available Elizabeth C Hersch, George R MerriamVA Puget Sound Health Care System and University of Washington School of Medicine, Tacoma and Seattle, Washington USAAbstract: Although growth hormone (GH is primarily associated with linear growth in childhood, it continues to have important metabolic functions in adult life. Adult GH deficiency (AGHD is a distinct clinical entity, and GH replacement in AGHD can improve body composition, strength, aerobic capacity, and mood, and may reduce vascular disease risk. While there are some hormone-related side effects, the balance of benefits and risks is generally favorable, and several countries have approved GH for clinical use in AGHD. GH secretion declines progressively and markedly with aging, and many age-related changes resemble those of partial AGHD. This suggests that replacing GH, or stimulating GH with GH-releasing hormone or a GH secretagogue could confer benefits in normal aging similar to those observed in AGHD – in particular, could reduce the loss of muscle mass, strength, and exercise capacity leading to frailty, thereby prolonging the ability to live independently. However, while most GH studies have shown body composition effects similar to those in AGHD, functional changes have been much less inconsistent, and older adults are more sensitive to GH side effects. Preliminary reports of improved cognition are encouraging, but the overall balance of benefits and risks of GH supplementation in normal aging remains uncertain.Keywords: growth hormone, growth hormone-releasing hormone, growth hormone secretagogues, aging, sarcopenia, frailty

  6. The Growth Hormone Secretagogue Receptor: Its Intracellular Signaling and Regulation

    Directory of Open Access Journals (Sweden)

    Yue Yin

    2014-03-01

    Full Text Available The growth hormone secretagogue receptor (GHSR, also known as the ghrelin receptor, is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase of food intake and body weight, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. Dependent on the tissues and cells, activation of GHSR may trigger a diversity of signaling mechanisms and subsequent distinct physiological responses. Distinct regulation of GHSR occurs at levels of transcription, receptor interaction and internalization. Here we review the current understanding on the intracellular signaling pathways of GHSR and its modulation. An overview of the molecular structure of GHSR is presented first, followed by the discussion on its signaling mechanisms. Finally, potential mechanisms regulating GHSR are reviewed.

  7. Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

    Science.gov (United States)

    Sawchenko, P. E.; Arias, C.; Krasnov, I.; Grindeland, R. E.; Vale, W.

    1992-01-01

    Possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion were investigated in rats flown on Cosmos 1887 and 2044 biosatellites. Immunohistochemical (IHC)staining for the growth hormone-releasing factor (GRF), somatostatin (SS), and other hypothalamic hormones was performed on hypothalami obtained from rats. IHC analysis was complemented by quantitative in situ assessments of mRNAs encoding the precursors for these hormones. Data obtained suggest that exposure to microgravity causes a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impared GH secretion in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

  8. Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics.

    Science.gov (United States)

    Tagliavini, Alessia; Tabak, Joël; Bertram, Richard; Pedersen, Morten Gram

    2016-04-01

    Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent Ca(2+) influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of Ca(2+) fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells. In this work, we apply computer simulations to test this hypothesis. We use experimental recordings of electrical activity as input to mathematical models of Ca(2+) channel activity, buffered Ca(2+) diffusion, and Ca(2+)-driven exocytosis. To compare the efficacy of spiking and bursting on the same cell, we pharmacologically block the large-conductance potassium (BK) current from a bursting cell or add a BK current to a spiking cell via dynamic clamp. We find that bursting is generally at least as effective as spiking at evoking hormone release and is often considerably more effective, even when normalizing to Ca(2+) influx. Our hybrid experimental/modeling approach confirms that adding a BK-type K(+) current, which is typically associated with decreased cell activity and reduced secretion, can actually produce an increase in hormone secretion, as suggested earlier.

  9. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

    Institute of Scientific and Technical Information of China (English)

    Haluk Kelestimur; Emine Kacar; Aysegul Uzun; Mete Ozcan; Selim Kutlu

    2013-01-01

    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

  10. Effects of age, weight, hormones, and hibernation on breeding success in boreal toads (Bufo boreas boreas).

    Science.gov (United States)

    Roth, T L; Szymanski, D C; Keyster, E D

    2010-03-01

    The goals of this study were to test the effects of exogenous hormones and hibernation on breeding behavior and gamete release by boreal toads (Bufo boreas boreas). Each year, a subset of 77 toads was hibernated and then paired with hibernated or nonhibernated mates and treated with luteinizing hormone releasing hormone analogue (LHRHa), human chorionic gonadotropin (hCG), or left untreated. Amplexus and egg and sperm production were recorded. At 1 yr of age, only 19% of pairs exhibited amplexus, and no sperm or eggs were produced. At 2 and 3 yr of age, most male toads treated with LHRHa exhibited amplexus (56.9% and 100%, respectively). Among 2-yr-old males, amplexus was more prevalent (Pbreeding success, males should be hibernated and treated with LHRHa. In contrast, female productivity was enhanced by improving their body condition instead of subjecting them to hibernation prior to LHRHa treatment.

  11. Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy

    Directory of Open Access Journals (Sweden)

    Bedimo R

    2011-07-01

    Full Text Available Roger BedimoInfectious Disease section, VA North Texas Health Care System, TX, USAAbstract: HIV-infected patients on highly active antiretroviral therapy (HAART develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy and central fat accumulation (lipohypertrophy. These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options – including antiretroviral switch, insulin sensitizers, and surgical approaches – have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog for the management of central fat accumulation. Randomized controlled trials have shown that administration of tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients. This effect is transient, however, and its association with improved cardiovascular risk remains unclear.Keywords: HAART, HIV, tesamorelin, lipodystrophy

  12. Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

    Science.gov (United States)

    Tappa, Karthik; Jammalamadaka, Udayabhanu; Ballard, David H; Bruno, Todd; Israel, Marissa R; Vemula, Harika; Meacham, J Mark; Mills, David K; Woodard, Pamela K; Weisman, Jeffery A

    2017-01-01

    3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

  13. A brief review on microfluidic platforms for hormones detection.

    Science.gov (United States)

    Ozhikandathil, Jayan; Badilescu, Simona; Packirisamy, Muthukumaran

    2017-01-01

    Lab-on-chip technology is attracting great interest due to its potential as miniaturized devices that can automate and integrate many sample-handling steps, minimize consumption of reagent and samples, have short processing time and enable multiplexed analysis. Microfluidic devices have demonstrated their potential for a broad range of applications in life sciences, including point-of-care diagnostics and personalized medicine, based on the routine diagnosis of levels of hormones, cancer markers, and various metabolic products in blood, serum, etc. Microfluidics offers an adaptable platform that can facilitate cell culture as well as monitor their activity and control the cellular environment. Signaling molecules released from cells such as neurotransmitters and hormones are important in assessing the health of cells and the effect of drugs on their functions. In this review, we provide an insight into the state-of-art applications of microfluidics for monitoring of hormones released by cells. In our works, we have demonstrated efficient detection methods for bovine growth hormones using nano and microphotonics integrated microfluidics devices. The bovine growth hormone can be used as a growth promoter in dairy farming to enhance the milk and meat production. In the recent years, a few attempts have been reported on developing very sensitive, fast and low-cost methods of detection of bovine growth hormone using micro devices. This paper reviews the current state-of-art of detection and analysis of hormone using integrated optical micro and nanofluidics systems. In addition, the paper also focuses on various lab-on-a-chip technologies reported recently, and their benefits for screening growth hormones in milk.

  14. Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

    Science.gov (United States)

    Childs, G V

    2002-04-01

    The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

  15. Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications.

    Science.gov (United States)

    Seminara, Stephanie B; Dipietro, Meloni J; Ramaswamy, Suresh; Crowley, William F; Plant, Tony M

    2006-05-01

    The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in three agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 microg human (hu) metastin 45-54 (equivalent to kisspeptin 112-121), the GPR54 agonist was infused continuously at a dose of 100 microg/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous drop in LH despite continuous exposure of GPR54 to metastin 45-54. On d 4, during the final 3 h of the infusion, single boluses of hu metastin 45-54 (10 microg), N-methyl-DL-aspartic acid (NMDA) (10 mg/kg) and GnRH (0.3 microg) were administered to interrogate each element of the metastin-GPR54-GnRH-GnRH receptor cascade. Although the NMDA and GnRH boluses were able to elicit LH pulses, that of hu metastin 45-54 was not, demonstrating functional integrity of GnRH neurons (NMDA) and GnRH receptors (NMDA and GnRH) but desensitization of GPR54. The desensitization of GPR54 by continuous hu metastin 45-54 administration has therapeutic implications for a variety of conditions currently being treated by GnRH and its analogs, including restoration of fertility in patients with abnormal GnRH secretion (i.e. idiopathic hypogonadotropic hypogonadism and hypothalamic amenorrhea) and selective, reversible suppression of the pituitary-gonadal axis to achieve suppression of gonadal steroids (i.e. precocious puberty, endometriosis, uterine fibroids, and prostate cancer).

  16. Pesticide exposure: the hormonal function of the female reproductive system disrupted?

    Directory of Open Access Journals (Sweden)

    Zielhuis Gerhard A

    2006-05-01

    Full Text Available Abstract Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as

  17. 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.

  18. Hormonal contraception and risk of venous thromboembolism: national follow-up study

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Løkkegaard, Ellen; Svendsen, Anne Louise

    2009-01-01

    and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any......OBJECTIVE: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. DESIGN: National cohort study. SETTING: Denmark, 1995-2005. PARTICIPANTS: Danish women aged 15.......4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3...

  19. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  20. Hormone impostors

    Energy Technology Data Exchange (ETDEWEB)

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  1. Controlled release of the pineal hormone melatonin from hydroxypropylmethylcellulose/sodium alginate matrices in aqueous media containing dioctyl sulfosuccinate.

    Science.gov (United States)

    Vlachou, Marilena; Tsiakoulia, Athanasia; Eikosipentaki, Aphrodite

    2007-06-01

    An investigation of the controlled release profile of mono-layered formulations of the hormone melatonin in modified aqueous media is described. The tablets used were comprised of hydroxypropylmethylcellulose (HPMC K15M) and sodium alginate with melatonin (fully soluble in the dioctyl sulfosuccinate (DSS) containing simulated intestinal solution). Three different sets of tablets (diameters 7.5, 10.0 and 13.0 mm) were tested with respect to the influence of their sizes on the hormone's release; the general trend observed was that tablets with larger surface area values had lower % release. A decrease in the value of W(o), obtained from the ratio [H(2)O]/[DSS], results to the predominance of DSS conformers in the aqueous media, which are less likely to solubilize melatonin effectively.

  2. Benefits and risks of hormonal contraception for women

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2007-08-01

    contraception. Headache appeared mostly only at the beginning of the use of combined oral contraceptives. Progestogen-only contraceptives worsened the results of the glucose tolerance test. A review of low evidence reported further risks of hormonal contraceptives (concerning menstrual problems, ovarian cysts, bone density, thyroid diseases and rheumatoid arthritis as well as further benefits (concerning blood pressure and Crohn’s disease. Hormonal spirals were shown to be more effective than spirals which do not release hormones. In emergency contraception, Levonorgestrel was more effective than the Yuzpe method. Most other proven differences between hormonal contraceptives were related to menstrual problems. After spirals with or without hormone release, the other hormonal contraceptives were shown in typical use to be the second most cost-effective reversible methods of contraception. Discussion: The addressed questions could be answered only on relatively low evidence level, partly only for applications with estrogen doses which are not used in Germany any more. The transferability of the results of the analysed primary health-economics studies on the current situation in Germany is limited (clinical assumptions from out-dated information sources of low evidence levels, cost assumptions from the American health system. Conclusions: In perfect use, hormonal contraceptives have to be classified as the most effective reversible contraceptive methods. For the individual decision concerning the use of hormonal contraception, benefits should be related to the additional risks. Alternative methods such as spirals should be prioritised if perfect use seems to be impossible. In this case, spirals are also preferable from health-economics perspective. No ethical-social or legal conclusions can be derived from the available data.

  3. [Glutamate neurotransmission, stress and hormone secretion].

    Science.gov (United States)

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

    Glutamate neurotransmission has been investigated in relation to several physiological processes (learning, memory) as well as to neurodegenerative and other disorders. Little attention has been paid to its involvement in neuroendocrine response during stress. Penetration of excitatory amino acids from blood to the brain is limited by the blood-brain barrier. As a consequence, several toxic effects but also bioavailability for therapeutic purposes are reduced. A free access to circulating glutamate is possible only in brain structures lacking the blood-brain barrier or under conditions of its increased permeability. Excitatory amino acids were shown to stimulate the pituitary hormone release, though the mechanism of their action is still not fully understood. Stress exposure in experimental animals induced specific changes in mRNA levels coding the glutamate receptor subunits in the hippocampus and hypothalamus. The results obtained with the use of glutamate receptor antagonists indicate that a number of specific receptor subtypes contribute to the stimulation of ACTH release during stress. The authors provided also data on the role of NMDA receptors in the control of catecholamine release, particularly in stress-induced secretion of epinephrine. These results were the first piece of evidence on the involvement of endogenous excitatory amino acids in neuroendocrine activation during stress. Neurotoxic effects of glutamate in animals are well described, especially after its administration in the neonatal period. In men, glutamate toxicity and its use as a food additive are a continuous subject of discussions. The authors found an increase in plasma cortisol and norepinephrine, but not epinephrine and prolactin, in response to the administration of a high dose of glutamate. It cannot be excluded that these effects might be induced even by lower doses in situations with increased vulnerability to glutamate action (age, individual variability). (Tab. 1, Fig. 6, Ref. 44.).

  4. Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

    Directory of Open Access Journals (Sweden)

    Armelle Tchoumi Neree

    2015-11-01

    Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

  5. Stimulatory and inhibitory effects of neuropeptide Y on growth hormone secretion in acromegaly in vivo.

    Science.gov (United States)

    Watanobe, H; Tamura, T

    1997-02-01

    It has been reported that neuropeptide Y (NPY) affects growth hormone (GH) secretion in several animal species. With respect to the role of NPY in regulating GH release in humans, one previous study has reported that NPY inhibited GH secretion from cultured GH-secreting pituitary adenoma cells in vitro. However, since it has yet to be explored whether NPY affects GH secretion in acromegaly in vivo, in this study we attempted to examine the effect of intravenous (i.v.) bolus injection of 100 microg of human NPY on plasma GH levels in 15 patients with active acromegaly, trying to find a possible correlation among GH responses to NPY, thyrotropin-releasing hormone (TRH;500 microg, i.v.), luteinizing hormone-releasing hormone (LHRH;100 microg, i.v.), and bromocriptine (Br;2.5 mg, per os). NPY significantly increased GH secretion (more than twice the basal level) in 4 (27%) patients, and all of them were responsive to LHRH and non-responsive to Br. In contrast, 3 (20%) acromegalics showed a significant decrease in GH levels (less than half the baseline) after NPY, and all these patients were responsive to both TRH and Br. From these results, we hypothesize that the NPY-induced increase in GH release may be a feature of somatotroph-like pituitary adenoma causing acromegaly, whereas the NPY-induced decrease in GH secretion may be a feature of lactotroph-like adenoma.

  6. Doping control analysis of selected peptide hormones using LC-MS(/MS).

    Science.gov (United States)

    Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

    2011-12-10

    With the constantly increasing sensitivity and robustness of liquid chromatography-mass spectrometry-based instruments combined with enhanced reproducibility as well as mass accuracy and resolution, LC-MS(/MS) has become an integral part of sports drug testing programs particularly concerning the detection of peptide hormones. Although several of the relevant peptidic drugs such as insulins (Humalog LisPro, Novolog Aspart, etc.), growth hormone releasing peptides (GHRPs, e.g., GHRP-2, GHRP-6, Hexarelin, etc.), and insulin-like growth factors (e.g., IGF-1, IGF-2, long-R(3)-IGF-1) are currently analyzed using dedicated top-down analytical procedures, i.e. employing specifically tailored sample preparation procedures followed by targeted LC-MS(/MS) measurements focusing on intact analytes, first approaches towards multi-analyte methods have been established. These allow the determination of the prohibited substances in blood and urine doping control specimens following therapeutic applications. In addition, the use of new complementary devices such as ion mobility analyzers, e.g., in hybrid mass spectrometers yielded promising data for the differentiation of isobaric insulins, which outlines the potential to further accelerate and multiplex doping control analytical assays to meet the continuously increasing demands of rapid and unambiguous test methods. Moreover, the potential of LC-MS/MS to target recombinant peptide hormones such as human growth hormone using bottom-up approaches has been demonstrated by targeting proteotypic peptides that unambiguously differentiate the recombinant molecule from the naturally occurring and endogenously produced analog.

  7. GPCR Interaction: 208 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Information about hetero oligomer between secretin receptor (SecR) and growth horm...one releasing hormone (GHRH), and interfaces of SecR C Secretin ... SecR C Growth hormone releasing hormone ... GH

  8. GPCR Interaction: 209 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available Information about hetero oligomer between growth hormone releasing hormone (GHRH) and secr...etin receptor (SecR), and interfaces of GNRH B Growth hormone releasing hormone ... GHRH C Secretin ... Se

  9. Effects of TCDD on thyroid hormone homeostasis in the rat.

    Science.gov (United States)

    Kohn, M C

    2000-02-01

    A physiological dosimetric model was constructed to describe the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on circulating thyroid hormones in the rat and to test the hypothesis that these hormonal changes cause chronically elevated serum thyrotropin (thyroid stimulating hormone, TSH), which mediates growth promotion and may lead to thyroid tumors in TCDD-treated rats. The model included diffusion restricted distribution of TCDD among compartments for liver, kidney, white fat, slowly and rapidly perfused tissues, and the thyroxine-sensitive tissues brown fat, pituitary, and thyroid. Blood was distributed among major vessels and the capillary beds of the tissues. Metabolism of TCDD was limited to the liver. Secretion of 3,5,3'-triiodothyronine (T3) and thyroxine (3,5,3',5'-tetraiodothyronine, T4) from the thyroid was modeled as stimulated by circulating TSH, whose release from the pituitary was regulated by the hypothalamic peptides thyrotropin releasing hormone (activating) and somatostatin (inhibiting). Release of these peptides was represented as inhibited and activated, respectively, by circulating T4. Binding proteins for T3 and T4 and metabolism of the hormones by deiodination were included in thyroxine-sensitive tissues. Induction of hepatic UDP-glucuronosyltransferase-1*6 (UGT), the enzyme which glucuronidates T4, was modeled as induced by the complex formed between TCDD and the aryl hydrocarbon receptor. The computed extent of deiodination, primacy of the thyroid in generating T3 from T4, dependence of liver and kidney on locally produced T3, and export of T3 formed in the pituitary agreed with experimental observations. The model reproduced the observed decrease in circulating T4 and elevated serum TSH following chronic administration of TCDD. The altered levels were attributed to the increased clearance of T4 by the induced UGT and the consequent modification of feedback control of hormone releases. These results are consistent with the

  10. The Growth Hormone Secretagogue Hexarelin Protects Rat Cardiomyocytes From in vivo Ischemia/Reperfusion Injury Through Interleukin-1 Signaling Pathway.

    Science.gov (United States)

    Huang, Jiannan; Li, Yi; Zhang, Juan; Liu, Yusheng; Lu, Qinghua

    2017-04-06

    Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion. The rats were then treated subcutaneously twice daily with hexarelin [100 μg/kg·day], ghrelin [400 μg/ kg·day], or saline for 7 days. Echocardiography, malondialdehyde detection, and histochemical staining were performed after treatment. In addition, Western blot was used to examine the expression levels of IL-1β, IL-1Ra, and IL-1RI. Our study showed that hexarelin treatment improved cardiac systolic function, decreased malondialdehyde production, and increased the number of surviving cardiomyocytes. The beneficial effects of hexarelin treatment were slightly superior to those of equimolar ghrelin treatment. We meanwhile confirmed that hexarelin induced down-regulation of IL-1β expression and up-regulation of IL-1Ra expression in I/R myocardium, which could be neutralized by the GHSR antagonist [D-Lys3]-growth hormone releasing peptide-6 ([D-Lys3]-GHRP-6). These findings suggest that hexarelin protects in vivo cardiomyocytes from I/R injury partly by modification of the IL-1 signaling pathway through the activation of cardiac GHSR1a receptors.

  11. Growth hormone suppression test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production ...

  12. Growth hormone test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003706.htm Growth hormone test To use the sharing features on this page, please enable JavaScript. The growth hormone test measures the amount of growth hormone ...

  13. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  14. Sleep and Endocrinology: Hypothalamic-pituitary- adrenal axis and growth hormone

    Directory of Open Access Journals (Sweden)

    Ravinder Goswami

    2014-03-01

    Full Text Available The supra-chiasmatic nucleus (SCN is the primarily biological clock determining thecircadian rhythm. The neurons of the nucleus making this clock have inherent rhythmand set in biological day and night. These periods usually corresponds to day/night, andindirectly to sleep-wakefulness cycle, in most individuals. Retino-hypothalamic tractcarrying photic information from the retina provides the most important input tomaintain the inherent rhythm of the SCN. The rhythmic discharges from the SCN tovarious neurons of the central nervous system, including pineal gland andhypothalamus, translate into circadian rhythm characteristic of several hormones andmetabolites such as glucose. As a result there is a pattern of hormonal changesoccurring during cycle of sleep wakefulness. Most characteristic of these changes aresurge of melatonin with biological night, surge of growth hormone-releasing hormone(GHRHat onset of sleep and surge of corticotropin-releasinghormone(CRHduring late part of the sleep. The cause and effect relationship of the hypothalamicreleasing hormones and their target hormones on various phases of sleep includinginitial non rapid eye movement (NREM phase at onset of sleep, and rapid eyemovement (REM phase near awakening, is an upcoming research area. Sleepelectroencephalogram (EEG determining the onset of NREM and REM sleep is animportant tool complimenting the studies assessing relationship between varioushormones and phases of sleep. The slow wave activity (SWA corresponds to theintensity of sleep at its onset during the biological night of an individual. Besides,GHRH and CRH, several other peptide and steroid hormones such as growthhormone (GH, its secretagogues, ghrelin, neuropeptide Y, estrogen anddehydroepiandrosterone sulfate are associated or have the potential to change phases ofsleep including initial slow wave-NREM sleep.

  15. NCBI nr-aa BLAST: CBRC-DNOV-01-2844 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2844 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-126 58% ...

  16. NCBI nr-aa BLAST: CBRC-CJAC-01-1513 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CJAC-01-1513 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 0.0 80% ...

  17. NCBI nr-aa BLAST: CBRC-TSYR-01-0231 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TSYR-01-0231 ref|NP_001003685.2| growth hormone releasing hormone receptor pre...cursor [Mus musculus] gb|AAI20749.1| Growth hormone releasing hormone receptor [Mus musculus] gb|AAI20775.1| Growth hormone... releasing hormone receptor [Mus musculus] NP_001003685.2 1e-134 62% ...

  18. NCBI nr-aa BLAST: CBRC-DRER-12-0072 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-12-0072 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-119 57% ...

  19. NCBI nr-aa BLAST: CBRC-HSAP-07-0017 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-07-0017 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 0.0 86% ...

  20. NCBI nr-aa BLAST: CBRC-LAFR-01-0274 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-LAFR-01-0274 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-106 84% ...

  1. NCBI nr-aa BLAST: CBRC-OLAT-04-0021 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-04-0021 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-110 52% ...

  2. NCBI nr-aa BLAST: CBRC-EEUR-01-0660 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-0660 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-129 83% ...

  3. NCBI nr-aa BLAST: CBRC-CPOR-01-2037 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CPOR-01-2037 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-110 73% ...

  4. NCBI nr-aa BLAST: CBRC-GGAL-02-0000 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-02-0000 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-148 58% ...

  5. NCBI nr-aa BLAST: CBRC-RMAC-03-0036 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RMAC-03-0036 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-138 72% ...

  6. NCBI nr-aa BLAST: CBRC-BTAU-01-2615 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-2615 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 0.0 82% ...

  7. NCBI nr-aa BLAST: CBRC-PTRO-08-0019 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-08-0019 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-141 60% ...

  8. NCBI nr-aa BLAST: CBRC-TGUT-04-0018 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-04-0018 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-147 60% ...

  9. NCBI nr-aa BLAST: CBRC-FCAT-01-0862 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FCAT-01-0862 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-179 79% ...

  10. NCBI nr-aa BLAST: CBRC-CFAM-14-0059 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-14-0059 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 0.0 89% ...

  11. NCBI nr-aa BLAST: CBRC-PABE-08-0029 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-08-0029 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 0.0 80% ...

  12. NCBI nr-aa BLAST: CBRC-FRUB-02-0138 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FRUB-02-0138 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-120 54% ...

  13. NCBI nr-aa BLAST: CBRC-ACAR-01-0764 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0764 ref|NP_999200.1| growth hormone releasing hormone receptor [Sus s...crofa] sp|P34999|GHRHR_PIG Growth hormone-releasing hormone receptor precursor (GHRH receptor) (GRF receptor...) (GRFR) gb|AAA93391.1| growth hormone-releasing hormone receptor NP_999200.1 1e-141 56% ...

  14. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.

    2017-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime, es

  15. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Budziszewska, B.; Tolmacheva, E.A.

    2009-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime, es

  16. Circulating nucleic acids in the assessment of endogenous growth hormone production.

    Science.gov (United States)

    Thakkar, H; Butt, A N; Powrie, J; Holt, R; Swaminathan, R

    2008-08-01

    There is growing concern about the use of recombinant human growth hormone (rhGH) by individuals taking part in competitive sports. Although rhGH is banned by the international organizations, the detection of GH doping is difficult. We postulated that rhGH will suppress endogenous GH production, which can be assessed by the measurement of mRNA for GH and growth hormone-releasing hormone (GHRH). In order to prove this concept, we undertook a pilot study to examine whether circulating nucleic acids are useful in the detection of endogenous GH production. Blood samples were collected into PAXgene tubes from 37 healthy controls and 12 acromegalic patients. RNA was extracted from the samples, cDNA was obtained, and the quantities of mRNA for GH and GHRH were measured using real-time PCR. In acromegalic patients, median mRNA concentration for GHRH (corrected for beta-actin mRNA) was 30.7 times lower than in controls (median delta C(T)) value of -0.128 versus 3.927, P 50 years) compared to the younger age group (<34 years). These results show that mRNA for GH and GHRH can be detected in the peripheral circulation and raises the possibility of using these markers in the detection of exogenously administered GH.

  17. EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments.

    Science.gov (United States)

    Baud, V; Chissoe, S L; Viegas-Péquignot, E; Diriong, S; N'Guyen, V C; Roe, B A; Lipinski, M

    1995-03-20

    Proteins with seven transmembrane segments (7TM) define a superfamily of receptors (7TM receptors) sharing the same topology: an extracellular N-terminus, three extramembranous loops on either side of the plasma membrane, and a cytoplasmic C-terminal tail. Upon ligand binding, cytoplasmic portions of the activated receptor interact with heterotrimeric G-coupled proteins to induce various second messengers. A small group, recently recognized on the basis of homologous primary amino acid sequences, comprises receptors to hormones of the secretin/vasoactive intestinal peptide/glucagon family, parathyroid hormone and parathyroid hormone-related peptides, growth hormone-releasing factor, corticotropin-releasing factor, and calcitonin. A cDNA, extracted from a neuroectodermal cDNA library, was predicted to encode a new 886-amino-acid protein with three distinct domains. The C-terminal third contains the seven hydrophobic segments and characteristic residues that allow the protein to be readily aligned with the various hormone receptors in the family. Six egf-like modules, at the N-terminus of the predicted mature protein, are separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Because of its unique characteristics, this putative egf module-containing, mucin-like hormone receptor has been named EMR1. Southern analysis of a panel of somatic cell hybrids and fluorescence in situ hybridization have assigned the EMR1 gene to human chromosome 19p13.3.

  18. Stress and the timing of breeding: glucocorticoid-luteinizing hormones relationships in an arctic seabird.

    Science.gov (United States)

    Goutte, Aurélie; Angelier, Frédéric; Chastel, Céline Clément; Trouvé, Colette; Moe, Børge; Bech, Claus; Gabrielsen, Geir W; Chastel, Olivier

    2010-10-01

    In birds, stressful environmental conditions delay the timing of breeding but the underlying mechanisms are poorly understood. The stress hormone corticosterone appears to be a good candidate for mediating the decision to breed and when to start egg-laying, via a possible inhibition of luteinizing hormone (LH) and sex-steroids production. We used luteinizing hormone releasing hormone (LHRH) challenge in pre-laying male and female Black-legged kittiwakes (Rissa tridactyla) to test whether LH and testosterone secretion were depressed by elevated corticosterone levels. Females bearing high baseline corticosterone levels showed reduced baseline LH levels and a low ability to release LH, following LHRH challenge. Further, females bearing low baseline LH levels and elevated baseline corticosterone levels were more likely to skip breeding. However, non-breeding females were physiologically primed for breeding, since they mounted high LHRH-induced LH release. Egg-laying date was advanced in good body condition females but was unaffected by hormones secretion. In males, corticosterone levels had no effect on LH and/or testosterone secretion and did not affect their decision to breed. Interestingly, males with high LHRH-induced testosterone release bred early. Our study highlights clear sex-differences in the HPG sensitivity to stress hormones in pre-laying kittiwakes. Because females have to store body reserves and to build up the clutch, they would be more sensitive to stress than males. Moreover, intrasexual competition could force male kittiwakes to acquire reproductive readiness earlier in the season than females and to better resist environmental perturbations. We suggest that high testosterone releasing ability would mediate behavioural adjustments such as courtship feeding, which would stimulate early egg-laying in females.

  19. 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.

  20. Chitosan-nanoconjugated hormone nanoparticles for sustained surge of gonadotropins and enhanced reproductive output in female fish.

    Directory of Open Access Journals (Sweden)

    Mohd Ashraf Rather

    Full Text Available A controlled release delivery system helps to overcome the problem of short life of the leutinizing hormone releasing hormone (LHRH in blood and avoids use of multiple injections to enhance reproductive efficacy. Chitosan- and chitosan-gold nanoconjugates of salmon LHRH of desired size, dispersity and zeta potential were synthesized and evaluated at half the dose rate against full dose of bare LHRH for their reproductive efficacy in the female fish, Cyprinus carpio. Whereas injections of both the nanoconjugates induced controlled and sustained surge of the hormones with peak (P<0.01 at 24 hrs, surge due to bare LHRH reached its peak at 7 hrs and either remained at plateau or sharply declined thereafter. While the percentage of relative total eggs produced by fish were 130 and 67 per cent higher, that of fertilised eggs were 171 and 88 per cent higher on chitosan- and chitosan-gold nanoconjugates than bare LHRH. Chitosan nanoconjugates had a 13 per cent higher and chitosan gold preparation had a 9 per cent higher fertilization rate than bare LHRH. Histology of the ovaries also attested the pronounced effect of nanoparticles on reproductive output. This is the first report on use of chitosan-conjugated nanodelivery of gonadotropic hormone in fish.

  1. Management of Adult Growth Hormone Deficiency at Peking Union Medical College Hospital:A Survey among Physicians

    Institute of Scientific and Technical Information of China (English)

    Hong-bo Yang; Meng-qi Zhang; Hui Pan; Hui-juan Zhu

    2016-01-01

    Objective To evaluate physicians’ attitude and knowledge about the management of adult growth hormone deficiency (AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making. Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital, a major teaching hospital in Chinese Academy of Medical Sciences. Data of physicians’ educational background, clinical training, patient workload per year and continuing medical education in AGHD were collected. Factors associated with appropriate answers were further analyzed by multivariate regression models. Results One hundred and eighteen internal medicine residents, endocrine fellows, attending physicians and visiting physicians responded to the survey. Among them, 44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy. Moreover, 56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD. Logistic regression analysis of physician demographic data, educational background, and work experience found no consistent independent factors associated with better decision-making, other than continued medical education, that were associated with treatment choice. Conclusions The physicians’ reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence. High quality continued medical education is required to improve Chinese physician management of AGHD.

  2. Standardization of hormone determinations.

    Science.gov (United States)

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.

  3. 山羊生长激素释放激素(GHRH)和抑制素βA(INHβA)基因多态性%Polymorphism of Growth Hormone Releasing Hormone (GHRH) and InhibinβA (INHβA) Genes in Goat

    Institute of Scientific and Technical Information of China (English)

    张海军; 陈宏; 房兴堂; 张润锋; 鲍斌; 徐海霞

    2007-01-01

    用PCR-SSCP和测序技术研究了波尔山羊(Capra hircus)和徐淮白山羊(C.hircus)2个群体共147个个体生长激素释放激素(GHRH)和抑制素βA(INHβA)基因座位的单核苷酸多态性(single nucleotide polymorphisms,SNPs),结果表明,GHRH基因在第4411处(按GenBank登录号AF242855)丢失了一个碱基G,在2个山羊群体检测到3种基因型(AA、AB和BB);NHβA基因在第995处(按GenBank登录号U16239)丢失了一个碱基T,在2个山羊群体检测到2种基因型(AA和AB),没有检测到BB型个体.这2个位点的突变属首次在山羊中发现,并且均以A等位基因为优势等位基因.同时,计算了2个基因座的杂合度(H)、有效等位基因数(Ne)、多态信息含量(PIC)和固定指数(F).结果显示,在2个山羊群体中,2个基因座均符合Hardy-Weinberg平衡.

  4. Effects of theophylline infusion on the growth hormone (GH) and prolactin response to GH-releasing hormone administration in acromegaly.

    Science.gov (United States)

    Losa, M; Alba-Lopez, J; Schopohl, J; Sobiesczcyk, S; Chiodini, P G; Müller, O A; von Werder, K

    1988-10-01

    Since theophylline has been shown to blunt the GH response to growth hormone-releasing hormone (GHRH) in normal subjects, we investigated whether the same effect of theophylline administration could be reproduced in patients with active acromegaly. Ten acromegalic patients received on two different days 100 micrograms GHRH iv alone and the same GHRH dose during a constant infusion of theophylline (3.56 mg/min), beginning 2 h before GHRH administration. In the whole group theophylline did not affect basal GH secretion significantly (from a mean of 44.6 +/- 14.4 at 0 min to 41.8 +/- 13.5 ng/ml at 120 min). However, the amount of GH released after GHRH stimulation was lower when theophylline was concomitantly infused (7525 +/- 3709 ng min/ml vs. 12038 +/- 6337 ng min/ml; p less than 0.05). The inhibitory effect of theophylline was not homogeneous, since either marked or minimal reductions of the GHRH-stimulated GH secretion occurred. Serum PRL levels increased after GHRH administration in 6 patients and theophylline infusion had no influence upon this response. Peak GHRH levels were not different in both studies (14.9 +/- 1.7 and 17.1 +/- 4.0 ng/ml, respectively). Free fatty acid levels rose progressively during theophylline administration (from 0.66 +/- 0.10 at 0 min to 1.04 +/- 0.10 mEq/l at 240 min) and were significantly higher than after GHRH stimulation alone from 180 min up to the end of the test. Our results demonstrate that in active acromegaly theophylline blunts the GH response to GHRH, though this effect is not uniformly seen in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Ecdysteroids, juvenile hormone and insect neuropeptides: Recent successes and remaining major challenges.

    Science.gov (United States)

    De Loof, Arnold

    2008-01-01

    In the recent decade, tremendous progress has been realized in insect endocrinology as the result of the application of a variety of advanced methods in neuropeptidome- and receptor research. Hormones of which the existence had been shown by bioassays four decades ago, e.g. bursicon (a member of the glycoprotein hormone family) and pupariation factor (Neb-pyrokinin 2, a myotropin), could be identified, along with their respective receptors. In control of diurnal rhythms, clock genes got company from the neuropeptide Pigment Dispersing Factor (PDF), of which the receptor could also be identified. The discovery of Inka cells and their function in metamorphosis was a true hallmark. Analysis of the genomes of Caenorhabditis elegans, Drosophila melanogaster and Apis mellifera yielded about 75, 100 and 200 genes coding for putative signaling peptides, respectively, corresponding to approximately 57, 100 and 100 peptides of which the expression could already be proven by means of mass spectrometry. The comparative approach invertebrates-vertebrates recently yielded indications for the existence of counterparts in insects for prolactin, atrial natriuretic hormone and Growth Hormone Releasing Hormone (GRH). Substantial progress has been realized in identifying the Halloween genes, a membrane receptor(s) for ecdysteroids, a nuclear receptor for methylfarnesoate, and dozens of GPCRs for insect neuropeptides. The major remaining challenges concern the making match numerous orphan GPCRs with orphan peptidic ligands, and elucidating their functions. Furthermore, the endocrine control of growth, feeding-digestion, and of sexual differentiation, in particular of males, is still poorly understood. The finding that the prothoracic glands produce an autocrine factor with growth factor-like properties and secrete proteins necessitates a reevaluation of their role in development.

  6. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Hormones and Menopause Fact Sheet Bioidentical Hormones and Menopause January, 2012 Download PDFs English Espanol Editors Howard ... JoAnn Pinkerton, MD Richard Santen, MD What is menopause? Menopause is the time of life when monthly ...

  7. Growth hormone deficiency

    Science.gov (United States)

    ... dosage of the medicine. Serious side effects of growth hormone treatment are rare. Common side effects include: Headache Fluid ... years. The rate of growth then slowly decreases. Growth hormone therapy does not work for all children. Left untreated, ...

  8. Hormones and Obesity

    Science.gov (United States)

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  9. Combined quantification of corticotropin-releasing hormone, cortisol-to-cortisone ratio and progesterone by liquid chromatography-Tandem mass spectrometry in placental tissue.

    Science.gov (United States)

    Fahlbusch, Fabian B; Ruebner, Matthias; Rascher, Wolfgang; Rauh, Manfred

    2013-09-01

    With mid-gestation the production of placental corticotropin-releasing hormone (CRH) starts to steadily increase. The fetal peptide CRH excerts direct functions at the feto-maternal interface (vasodilatation, timing of birth) via its interaction with progesterone and indirectly ensures maturation and growth of fetal organ systems for delivery by driving fetal cortisol production via its induction of adrenocorticotropic hormone release. This feedback loop is tightly controlled by the amount of enzymatic cortisol/cortisone turnover in the placental syncytiotrophoblast by 11β-hydroxy-steroid dehydrogenase type 2 (11β-HSD2). Traditionally, placental tissue hormones have been quantified by immunological methods (e.g. RIA or ELISA), which have the drawback of possible cross-reactivity and tissue perturbations. Most importantly, it is not possible to quantify CRH and steroid hormones, such as cortisol, cortisone and progesterone together in the same sample with these methods. Hence, we aimed to develop and validate a quantitative mass spectrometry (MS) method for multi-modal quantification of these placental hormones: While CRH was readily detectable throughout the placenta, the placental levels of progesterone and especially cortisol and cortisone were higher at the placental base facing the maternal side. The HPLC-MS/MS procedure showed excellent selectivity and sufficient limit of quantification in placental tissue homogenates to allow for simultaneous detection of CRH, cortisol and cortisone, and progesterone. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 杏仁核内去甲肾上腺素在应激激素调控记忆保持过程中的作用%Role of amygdala norepinephrine in mediating stress hormone regu-lation of memory storage

    Institute of Scientific and Technical Information of China (English)

    Barbara FERRY; James L McGAUGH

    2000-01-01

    There is extensive evidence indicating that the noradrenergic system of the amygdala, particularly the basolateral nucleus of the amygdala (BLA), is involved in memory consolidation. This article reviews the central hypothesis that stress hormones released during emotionally arousing experiences activate noradrenergic mechanisms in the BLA, resulting in enhanced memory for those events. Findings from expenments using rats have shown that the memory-modulatory effects of the adrenocortical stress hormones epinephrine and glucocorficoids involve activation of β-adrenoceptors in the BLA. In addition, both behavioral and microdialysis studies have shown that the noradrenergic system of the BLA also mediates the influences of other neuromodulatory systems such as opioid peptidergic and GABAergic systems on memory storage. Other findings indicate that this stress hormone-induced activation of noradrenergic mechanisms in the BLA regulates memory storage in other brain regions.

  11. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    Science.gov (United States)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  12. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    Science.gov (United States)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  13. Properties of PLA/PCL particles as vehicles for oral delivery of the androgen hormone 17α-methyltestosterone.

    Science.gov (United States)

    Sacchetin, Priscila Soares Costa; Setti, Rafaela Ferreira; Vieira e Rosa, Paulo de Tarso; Moraes, Ângela Maria

    2016-01-01

    The aim of this study was to produce PLA (poly(lactic acid)) and PCL (polycaprolactone) oral carriers through the precipitation of the polymer solutions using supercritical CO2 as an antisolvent for the controlled release of the hydrophobic model drug 17α-methyltestosterone (MT). Such drug is a steroidal hormone used orally to develop and sustain primary and secondary male sex characteristics, e.g. for female Nile tilapia sex reversal in aquaculture. The influence of hormone, PLA and PCL concentrations on particle formation was analyzed, showing that high PCL concentrations produced particles with rougher surfaces and greater mean diameters. The incorporation efficiency of MT ranged from 20 to 51%, and its addition resulted in increases in particle mean diameter from 23 to 54 μm. Aggregation was observed for particles incorporating or not MT and high concentrations of MT led to the formation of more amorphous structures, changing the thermal behavior of the particles. The exposure of the PLA/PCL particles to pH conditions simulating gastrointestinal fish conditions showed that hormone release fraction at acidic pH ranged from 8 to 63% (over 2h), while in the basic pH the proportion released varied from 23 to 60% (over 10h), reaching levels adequate for the desired in vivo activity.

  14. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Directory of Open Access Journals (Sweden)

    Kim Nuytens

    Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  15. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Science.gov (United States)

    Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

    2014-01-01

    Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  16. Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Ömer Tarım

    2010-05-01

    Full Text Available Growth hormone deficiency is the most promising entity in terms of response to therapy among the treatable causes of growth retardation. It may be due to genetic or acquired causes. It may be isolated or a part of multiple hormone deficiencies. Diagnostic criteria and therefore treatment indications are still disputed. (Journal of Current Pediatrics 2010; 8: 36-8

  17. Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway

    Energy Technology Data Exchange (ETDEWEB)

    Plosz, Benedek Gy., E-mail: benedek.plosz@niva.no [Norwegian Institute for Water Research, NIVA, Gaustadalleen 21, NO-0349, Oslo (Norway); Leknes, Henriette [Norwegian Institute for Air Research NILU, 2027 Kjeller (Norway); Liltved, Helge; Thomas, Kevin V. [Norwegian Institute for Water Research, NIVA, Gaustadalleen 21, NO-0349, Oslo (Norway)

    2010-03-15

    We present an assessment of the dynamics in the influent concentration of hormones (estrone, estriol) and antibiotics (trimethoprim, sulfamethoxazole, tetracycline, ciprofloxacin) in the liquid phase including the efficiency of biological municipal wastewater treatment. The concentration of estradiol, 17-{alpha}-ethinylestradiol, doxycycline, oxytetracycline, demeclocycline, chlortetracycline, cefuroxime, cyclophosphamide, and ifosfamide were below the limit of detection in all of the sewage samples collected within this study. Two different types of diurnal variation pattern were identified in the influent mass loads of selected antibiotics and hormones that effectively correlate with daily drug administration patterns and with the expected maximum human hormone release, respectively. The occurrence of natural hormones and antimicrobials, administered every 12 hours, shows a daily trend of decreasing contaminant mass load, having the maximum values in the morning hours. The occurrence of antibiotics, typically administered every 8 hours, indicates a daily peak value in samples collected under the highest hydraulic loading. The efficiency of biological removal of both hormones and antibiotics is shown to be limited. Compared to the values obtained in the influent samples, increased concentrations are observed in the biologically treated effluent for trimethoprim, sulfamethoxazole and ciprofloxacin, mainly as a result of deconjugation processes. Ciprofloxacin is shown as the predominant antimicrobial compound in the effluent, and it is present at quantities approximately 10 fold greater than the total mass of the other of the compounds due to poor removal efficiency and alternating solid-liquid partitioning behaviour. Our results suggest that, to increase the micro-pollutant removal and the chemical dosing efficiency in enhanced tertiary treatment, significant benefits can be derived from the optimisation of reactor design and the development of control schemes that

  18. Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway.

    Science.gov (United States)

    Plósz, Benedek Gy; Leknes, Henriette; Liltved, Helge; Thomas, Kevin V

    2010-03-15

    We present an assessment of the dynamics in the influent concentration of hormones (estrone, estriol) and antibiotics (trimethoprim, sulfamethoxazole, tetracycline, ciprofloxacin) in the liquid phase including the efficiency of biological municipal wastewater treatment. The concentration of estradiol, 17-alpha-ethinylestradiol, doxycycline, oxytetracycline, demeclocycline, chlortetracycline, cefuroxime, cyclophosphamide, and ifosfamide were below the limit of detection in all of the sewage samples collected within this study. Two different types of diurnal variation pattern were identified in the influent mass loads of selected antibiotics and hormones that effectively correlate with daily drug administration patterns and with the expected maximum human hormone release, respectively. The occurrence of natural hormones and antimicrobials, administered every 12 hours, shows a daily trend of decreasing contaminant mass load, having the maximum values in the morning hours. The occurrence of antibiotics, typically administered every 8 hours, indicates a daily peak value in samples collected under the highest hydraulic loading. The efficiency of biological removal of both hormones and antibiotics is shown to be limited. Compared to the values obtained in the influent samples, increased concentrations are observed in the biologically treated effluent for trimethoprim, sulfamethoxazole and ciprofloxacin, mainly as a result of deconjugation processes. Ciprofloxacin is shown as the predominant antimicrobial compound in the effluent, and it is present at quantities approximately 10 fold greater than the total mass of the other of the compounds due to poor removal efficiency and alternating solid-liquid partitioning behaviour. Our results suggest that, to increase the micro-pollutant removal and the chemical dosing efficiency in enhanced tertiary treatment, significant benefits can be derived from the optimisation of reactor design and the development of control schemes that

  19. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Juliana Austin

    2009-01-01

    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  20. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Austin Juliana

    2008-11-01

    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  1. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  2. Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole.

    Science.gov (United States)

    Carlson, Robert W; Henderson, I Craig

    2003-01-01

    The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that

  3. Aging changes in hormone production

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

  4. Hormones and female sexuality

    Directory of Open Access Journals (Sweden)

    Bjelica Artur L.

    2003-01-01

    Full Text Available Introduction In contrast to animal species in which linear relationships exist between hormonal status and sexual behaviour sexuality in human population is not determined so simply by the level of sexual steroids. The article analyses female sexuality in the light of hormonal status. Administration of sexual steroids during pregnancy and sexual differentiation High doses of gestagens, especially those with high androgen activity, widely used against miscarriages may lead to tomboys, but without differences in sexual orientation. However, it has been observed that the frequency of bisexual and lesbian women is higher in women with congenital adrenogenital syndrome. Hormones sexual desire and sexuality during menstrual cycle It has been established that sexual desire, autoeroticism and sexual fantasies in women depend on androgen levels. There are a lot of reports claiming that sexual desire varies during the menstrual cycle. Hormonal contraception and sexuality Most patients using birth control pills present with decreased libido. But, there are reports that progestagens with antiandrogenic effect in contraceptive pills do not affect sexual desire. Hormonal changes in peri- and postmenopausal period and sexuality Decreased levels of estrogen and testosterone in older women are associated with decreased libido, sensitivity and erotic stimuli. Sexuality and hormone replacement therapy Hormonal therapy with estrogen is efficient in reference to genital atrophy, but not to sexual desire. Really increased libido is achieved using androgens. Also, therapy with dehydroepiandrosterone (DHEA and tibolone have positive effects on female libido. Conclusion Effect of sexual steroids on sexual sphere of women is very complex. The association between hormones and sexuality is multidimensional, as several hormones are important in regulation of sexual behaviour. Still, it should be pointed out that sexuality is in the domain of hormonal, emotional

  5. Migraine and Hormones.

    Science.gov (United States)

    Pakalnis, Ann

    2016-02-01

    This article discusses the role that hormones play in adolescent girls and young women with headaches, which are very common in adolescent girls, in particular, migraine. In many cases, migraine onset may occur shortly around the time of menarche, prevalence of recurrent migraine in this population approaches 15%, and typically the symptoms continue through adulthood. Hormonal changes associated with puberty and the menstrual cycle may significantly influence migraine in young women. This article reviews the following topics: management of menstrually related headaches, changes in ovarian hormones and their relationship to migraine, and oral contraceptives and pregnancy effects on migraine.

  6. LH (Luteinizing Hormone) Test

    Science.gov (United States)

    ... develop gonads (gonadal agenesis) Chromosomal abnormality, such as Klinefelter syndrome Testicular failure: Viral infection ( mumps ) Trauma Exposure to ... the ovaries or testicles Hormone deficiency Turner syndrome Klinefelter syndrome Chronic infections Cancer Eating disorder (anorexia nervosa) ^ Back ...

  7. Thyroid Hormone Treatment

    Science.gov (United States)

    ... need a different dose of thyroid hormone include birth control pills, estrogen, testosterone, some anti-seizure medications (for ... is no evidence that desiccated thyroid has any advantage over synthetic T4. WHAT ABOUT T3? While most ...

  8. Deciding about hormone therapy

    Science.gov (United States)

    ... your risk for endometrial cancer. Taking progestin with estrogen seems to protect against this cancer. So if you have a ... menopause without taking hormones. They can also help protect your bones, improve your heart health , and help you stay ...

  9. Menopause and Hormones

    Science.gov (United States)

    ... the participating organizations that have assisted in its reproduction and distribution. Learn More about Menopause and Hormones ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  10. Hormonal contraception and risk of venous thromboembolism: national follow-up study

    DEFF Research Database (Denmark)

    2009-01-01

    .001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.......22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1...... and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any...

  11. Hormones and female sexuality

    OpenAIRE

    2003-01-01

    Introduction In contrast to animal species in which linear relationships exist between hormonal status and sexual behaviour sexuality in human population is not determined so simply by the level of sexual steroids. The article analyses female sexuality in the light of hormonal status. Administration of sexual steroids during pregnancy and sexual differentiation High doses of gestagens, especially those with high androgen activity, widely used against miscarriages may lead to tomboys, but with...

  12. Hormonal Regulators of Appetite

    OpenAIRE

    Austin Juliana; Marks Daniel

    2008-01-01

    Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger a...

  13. Protein Hormones and Immunity‡

    Science.gov (United States)

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  14. Body segments and growth hormone.

    OpenAIRE

    Bundak, R; Hindmarsh, P C; Brook, C. G.

    1988-01-01

    The effects of human growth hormone treatment for five years on sitting height and subischial leg length of 35 prepubertal children with isolated growth hormone deficiency were investigated. Body segments reacted equally to treatment with human growth hormone; this is important when comparing the effect of growth hormone on the growth of children with skeletal dysplasias or after spinal irradiation.

  15. Treatment with thyroid hormone.

    Science.gov (United States)

    Biondi, Bernadette; Wartofsky, Leonard

    2014-06-01

    Thyroid hormone deficiency can have important repercussions. Treatment with thyroid hormone in replacement doses is essential in patients with hypothyroidism. In this review, we critically discuss the thyroid hormone formulations that are available and approaches to correct replacement therapy with thyroid hormone in primary and central hypothyroidism in different periods of life such as pregnancy, birth, infancy, childhood, and adolescence as well as in adult patients, the elderly, and in patients with comorbidities. Despite the frequent and long term use of l-T4, several studies have documented frequent under- and overtreatment during replacement therapy in hypothyroid patients. We assess the factors determining l-T4 requirements (sex, age, gender, menstrual status, body weight, and lean body mass), the major causes of failure to achieve optimal serum TSH levels in undertreated patients (poor patient compliance, timing of l-T4 administration, interferences with absorption, gastrointestinal diseases, and drugs), and the adverse consequences of unintentional TSH suppression in overtreated patients. Opinions differ regarding the treatment of mild thyroid hormone deficiency, and we examine the recent evidence favoring treatment of this condition. New data suggesting that combined therapy with T3 and T4 could be indicated in some patients with hypothyroidism are assessed, and the indications for TSH suppression with l-T4 in patients with euthyroid multinodular goiter and in those with differentiated thyroid cancer are reviewed. Lastly, we address the potential use of thyroid hormones or their analogs in obese patients and in severe cardiac diseases, dyslipidemia, and nonthyroidal illnesses.

  16. Changes in diurnal sympathoadrenal balance and pituitary hormone secretion in subjects with Leu7Pro polymorphism in the prepro-neuropeptide Y.

    Science.gov (United States)

    Kallio, Jaana; Pesonen, Ullamari; Jaakkola, Ulriikka; Karvonen, Matti K; Helenius, Hans; Koulu, Markku

    2003-07-01

    Neuropeptide Y (NPY) is an important neurotransmitter in the central and peripheral nervous systems. It has a regulatory role in cardiovascular and metabolic functions and control of hormone release. The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy. This study elucidated the role of this polymorphism in diurnal cardiovascular, metabolic, and hormonal functions of healthy subjects during rest. The two study groups comprised individuals with different genotype, but they were matched for age and body mass index. Subjects with the Leu7Pro polymorphism had significantly lower plasma NPY and norepinephrine concentrations, lower insulin concentrations, higher glucose concentrations, and lower insulin-glucose ratio in plasma than the controls. Heart rate was significantly higher during daytime in the subjects with Leu7Pro polymorphism. Furthermore, these subjects had significantly lower prolactin concentrations in plasma. Systolic and diastolic blood pressure, serum free fatty acid and plasma leptin, ACTH, cortisol, LH, FSH, TSH, free thyroxin, and melatonin concentrations were similar during the 24-h period, compared with controls. These results show that genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.

  17. Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone.

    Directory of Open Access Journals (Sweden)

    Jeroen Declercq

    Full Text Available The Nestin-Cre driver mouse line has mild hypopituitarism, reduced body weight, a metabolic phenotype and reduced anxiety. Although several causes have been suggested, a comprehensive explanation is still lacking. In this study we examined the molecular mechanisms leading to this compound phenotype. Upon generation of the Nestin-Cre mice, the human growth hormone (hGH minigene was inserted downstream of the Cre recombinase to ensure efficient transgene expression. As a result, hGH is expressed in the hypothalamus. This results in the auto/paracrine activation of the GH receptor as demonstrated by the increased phosphorylation of signal transducer and activator of transcription 5 (STAT5 and reduced expression of growth hormone releasing hormone (Ghrh. Low Ghrh levels cause hypopituitarism consistent with the observed mouse growth hormone (mGH deficiency. mGH deficiency caused reduced activation of the GH receptor and hence reduced phosphorylation of STAT5 in the liver. This led to decreased levels of hepatic Igf-1 mRNA and consequently postnatal growth retardation. Furthermore, genes involved in lipid uptake and synthesis, such as CD36 and very low-density lipoprotein receptor were upregulated, resulting in liver steatosis. In conclusion, this study demonstrates the unexpected expression of hGH in the hypothalamus of Nestin-Cre mice which is able to activate both the GH receptor and the prolactin receptor. Increased hypothalamic GH receptor signaling explains the observed hypopituitarism, reduced growth and metabolic phenotype of Nestin-Cre mice. Activation of either receptor is consistent with reduced anxiety.

  18. Correlation of thyroid hormone levels and immune function state with the illness in patients with chronic urticaria

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yan Sun; Guang-Zhong Yang; Qing-Xiang Li; Yao Wang

    2016-01-01

    Objective:To study the correlation of thyroid hormone level and immune function state with the illness in patients with chronic urticaria.Methods:A total of 54 patients with chronic urticaria treated in our hospital between May 2015 and October 2015 were selected as the chronic urticaria group (CU group) of the study, 50 healthy volunteers receiving physical examination in our hospital during the same period were selected as the negative control group (NC group) of the study, serum was collected to determine the content of immunoglobulins, complements, interleukins, thyroid hormone and autoantibodies.Results: Serum C3, C4 and IL-2 content of CU group were significantly lower than those of NC group while IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content were significantly higher than those of NC group; serum TT3, TT4, FT3, FT4, TSAb, TGAb, TPOAb and TMAb content of CU group were significantly higher than those of NC group, negatively correlated with serum C3, C4 and IL-2 content, and positively correlated with serum IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content;serum TSH content was significantly lower than that of NC group, positively correlated with serum C3, C4 and IL-2 content, and negatively correlated with serum IgG, IgE, IL-4, IL-17, IL-18 and IL-33 content.Conclusions: Thyroid autoantibody synthesis and thyroid hormone release increase in patients with chronic urticaria, and the change of thyroid hormone levels and immune function is closely related to the illness.

  19. Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis

    DEFF Research Database (Denmark)

    Støving, R K; Veldhuis, J D; Flyvbjerg, A;

    1999-01-01

    pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted...... and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were....... Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone....

  20. Headache And Hormones

    Directory of Open Access Journals (Sweden)

    Shukla Rakesh

    2002-01-01

    Full Text Available There are many reasons to suggest a link between headache and hormones. Migraine is three times common in women as compared to men after puberty, cyclic as well as non-cyclic fluctuations in sex hormone levels during the entire reproductive life span of a women are associated with changes in frequency or severity of migraine attack, abnormalities in the hypothalamus and pineal gland have been observed in cluster headache, oestrogens are useful in the treatment of menstrual migraine and the use of melatonin has been reported in various types of primary headaches. Headache associated with various endocrinological disorders may help us in a better understanding of the nociceptive mechanisms involved in headache disorders. Prospective studies using headache diaries to record the attacks of headache and menstrual cycle have clarified some of the myths associated with menstrual migraine. Although no change in the absolute levels of sex hormones have been reported, oestrogen withdrawal is the most likely trigger of the attacks. Prostaglandins, melatonin, opioid and serotonergic mechanisms may also have a role in the pathogenesis of menstrual migraine. Guidelines have been published by the IHS recently regarding the use of oral contraceptives by women with migraine and the risk of ischaemic strokes in migraineurs on hormone replacement therapy. The present review includes menstrual migraine, pregnancy and migraine, oral contraceptives and migraine, menopause and migraine as well as the hormonal changes in chronic migraine.

  1. Hormonal control of euryhalinity

    Science.gov (United States)

    Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  2. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  3. The effects of in ovo rhIGF-I administration on expression of the growth hormone secretagogue receptor (GHSR) during chicken embryonic development.

    Science.gov (United States)

    Gahr, Scott A; Kocamis, Hakan; Richter, Jennifer J; Killefer, John

    2004-01-01

    Growth hormone secretion is under the control of a pair of hypothalamic factors, growth hormone releasing hormone and somatostatin. The growth hormone secretagogue receptor (GHSR) and its endogenous ligand represent a novel third method regulating the release of growth hormone. Early chicken embryonic development has been proposed to be independent of GH. However, recent evidence shows that peripheral GH secretion has paracrine/autocrine functions during embryonic development. In the current study, we used the reverse-transcriptase polymerase chain reaction to determine the expression pattern of the GHSR during embryonic development and the effects of in ovo recombinant human (rh) IGF-I administration on its expression pattern. Eggs were injected once with 100 ng rhIGF-I in 10 mM acetic acid, and 0.1% BSA per embryo on embryonic day 3. Total RNA was isolated from whole embryos on embryonic day (E) 0-6 (n=6 per day), thoracic/abdominal halves of the embryos on E7- E8 (n= 6 per day) and Pectoralis muscle on E9-E20 (n= 4 per day). We found that GHSR expression was low during E0-E4, followed by an increase on E5 and remained constant through E17. GHSR expression then increased on E18 before reducing on E20. A similar pattern was found in the rhIGF-I treated embryos with the exception of a significant increase in GHSR expression on E8. These data indicate that the GHSR may be active in regulating GH secretion during early embryonic development, and upregulation of the GHSR gene following IGF-I administration may have an important role in the determination of postnatal muscle growth.

  4. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  5. Hormonal influences on osteoporosis.

    Science.gov (United States)

    McKenna, M J; Frame, B

    1987-01-26

    Osteoporosis has recently received increased attention in both the medical and lay literature. It is estimated that there are more than one million osteoporosis-related fractures yearly in the United States, which are responsible for between three and four billion dollars in health care expenditures. A discussion of osteoporosis requires consideration of both the physiology and pathophysiology of bone tissue. In a structural sense, bone exists in two forms, the outer compact cortex accounting for 80 percent of total bone volume, and the more porous inner trabecular bone. Bone-forming osteoblasts and bone-resorbing osteoclasts are responsible for the ongoing, life-long process of formation and resorption of bone. Sex hormone deficiency, as well as chronic illness, malnutrition, and childhood immobilization, has deleterious effects on growth and modeling, ultimately reducing peak bone mass and setting the stage for osteoporosis in later life. Estrogen is known to have a protective effect on the female skeleton. The mechanisms of this effect are unknown, although estrogen may protect against parathyroid hormone-mediated bone loss. There may be a particular subset of postmenopausal women who are particularly susceptible to estrogen deficiency. Calcitonin levels, which decrease postmenopausally, return to normal with estrogen; other hormones may also play important roles. Osteoporosis is not the result of a single hormonal deficiency or excess; it must be considered in relation to other pathogenetic and risk factors.

  6. [Adipose tissue hormones].

    Science.gov (United States)

    Haluzík, M; Trachta, P; Haluzíková, D

    2010-10-01

    Adipose tissue had been traditionally considered a passive energy storage site without direct influence on energy homeostasis regulation. This view has been principally changed during early nineties by the discovery of hormonal production of adipose tissue. At present, the list of hormonally active substances of adipose tissue includes more than one hundred factors with paracrine or endocrine activity that play an important role in metabolic, food intake a inflammatory regulations and many other processes. Only minority of adipose tissue-derived hormones is produced exclusively in fat. Most of these factors is primarily put out by other tissues and organs. Adipose tissue-derived hormones are produced not only by adipocytes but also by preadipocytes, immunocompetent and endothelial cells and other cell types residing in fat. This paper summarizes current knowledge about endocrine function of adipose tissue with special respect to its changes in obesity. It also describes its possible role in the ethiopathogenesis of insulin resistance, atherosclerosis and other obesity-related pathologies.

  7. Thyroid hormone deiodination

    NARCIS (Netherlands)

    T.J. Visser (Theo)

    1980-01-01

    textabstractThe enzymatic deiodination of thyroid hormone is an important process since it concerns- among other things- the regulation of thyromimetic activity at the site of the target organ. To understand the mechanism of this regulation it is necessary to have a detailed knowledge of the mode of

  8. Thyroid hormone deiodination

    NARCIS (Netherlands)

    T.J. Visser (Theo)

    1980-01-01

    textabstractThe enzymatic deiodination of thyroid hormone is an important process since it concerns- among other things- the regulation of thyromimetic activity at the site of the target organ. To understand the mechanism of this regulation it is necessary to have a detailed knowledge of the mode of

  9. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  10. Hormonal contraception and venous thromboembolism

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Milsom, Ian; Geirsson, Reynir Tomas;

    2012-01-01

    New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published.......New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published....

  11. Growth Hormone Deficiency in Adults

    Science.gov (United States)

    ... mass and strength Mild bone loss Thinning skin Sleep problems Decreased exercise performance Decreased energy Decreased well-being, mild depression, or moodiness What are the benefits of growth hormone therapy? Growth hormone treatment involves injections (shots) ...

  12. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  13. Growth Hormone Deficiency in Children

    Science.gov (United States)

    Fact Sheet Growth Defici H e o n r c m y one in Children What is growth hormone deficiency? Growth hormone deficiency (GHD) is a rare condition in which the body does not make enough growth hormone (GH). GH is made by the pituitary ...

  14. Hormonal Control of Fetal Growth.

    Science.gov (United States)

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  15. NCBI nr-aa BLAST: CBRC-GGOR-01-0759 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGOR-01-0759 ref|NP_000814.2| growth hormone releasing hormone receptor isofor...m a precursor [Homo sapiens] sp|Q02643|GHRHR_HUMAN RecName: Full=Growth hormone-releasing hormone receptor; ...Short=GHRH receptor; AltName: Full=GRF receptor; Short=GRFR; Flags: Precursor gb|AAA58619.1| growth hormone-releasing gormone... receptor [Homo sapiens] gb|AAC23789.1| growth hormone-releasing hormone... receptor [Homo sapiens] dbj|BAC05924.1| seven transmembrane helix receptor [Homo sapiens] gb|AAS59864.1| growth hormone

  16. NCBI nr-aa BLAST: CBRC-TTRU-01-1314 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-1314 ref|NP_000814.2| growth hormone releasing hormone receptor isofor...m a precursor [Homo sapiens] sp|Q02643|GHRHR_HUMAN RecName: Full=Growth hormone-releasing hormone receptor; ...Short=GHRH receptor; AltName: Full=GRF receptor; Short=GRFR; Flags: Precursor gb|AAA58619.1| growth hormone-releasing gormone... receptor [Homo sapiens] gb|AAC23789.1| growth hormone-releasing hormone... receptor [Homo sapiens] dbj|BAC05924.1| seven transmembrane helix receptor [Homo sapiens] gb|AAS59864.1| growth hormone

  17. NCBI nr-aa BLAST: CBRC-TSYR-01-0231 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TSYR-01-0231 ref|NP_000814.2| growth hormone releasing hormone receptor isofor...m a precursor [Homo sapiens] sp|Q02643|GHRHR_HUMAN RecName: Full=Growth hormone-releasing hormone receptor; ...Short=GHRH receptor; AltName: Full=GRF receptor; Short=GRFR; Flags: Precursor gb|AAA58619.1| growth hormone-releasing gormone... receptor [Homo sapiens] gb|AAC23789.1| growth hormone-releasing hormone... receptor [Homo sapiens] dbj|BAC05924.1| seven transmembrane helix receptor [Homo sapiens] gb|AAS59864.1| growth hormone

  18. NCBI nr-aa BLAST: CBRC-PCAP-01-0323 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PCAP-01-0323 ref|NP_000814.2| growth hormone releasing hormone receptor isofor...m a precursor [Homo sapiens] sp|Q02643|GHRHR_HUMAN RecName: Full=Growth hormone-releasing hormone receptor; ...Short=GHRH receptor; AltName: Full=GRF receptor; Short=GRFR; Flags: Precursor gb|AAA58619.1| growth hormone-...releasing gormone receptor [Homo sapiens] gb|AAC23789.1| growth hormone-releasing hormone... receptor [Homo sapiens] dbj|BAC05924.1| seven transmembrane helix receptor [Homo sapiens] gb|AAS59864.1| growth hormone

  19. Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease.

    Science.gov (United States)

    Aziz, N A; Pijl, H; Frölich, M; Roelfsema, F; Roos, R A C

    2011-06-01

    Recently, a massive loss of both hypocretin and melanin-concentrating hormone (MCH) neurones was found in the hypothalamus of Parkinson's disease (PD) patients. Because both hypocretin and MCH play a key role in the regulation of sleep, energy homeostasis and autonomic function, partly by modulation of the somatotrophic, thyrotrophic and lactotrophic axes, neuroendocrine dysregulation may contribute to some of the non-motor features of PD. In eight de novo, medication-free PD patients and eight age-, sex- and body mass index-matched controls, we measured serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH) and prolactin every 10 min for 24 h. Auto-deconvolution, cosinor and approximate entropy analysis were applied to quantify GH, TSH and prolactin secretion rates, diurnal rhythmicity, as well as regularity of hormone release. Sleep was polygraphically-recorded throughout the night. Total 24-h secretion of GH (191 ± 31 versus 130 ± 39 mU/l/24 h), TSH (38 ± 9 versus 36 ± 2 mU/l/24 h) and prolactin (102 ± 14 versus 116 ± 17 μg/l/24 h), as well as their diurnal rhythmicity and regularity of release, were not significantly different between PD patients and controls (all P ≥ 0.12). Fasting levels of insulin-like growth factor-1 were also unaltered in PD patients. However, free thyroxine (T(4) ) levels were significantly higher in PD patients compared to controls (16.19 ± 0.80 versus 13.88 ± 0.40 pmol/l; P = 0.031). In PD patients, prolactin levels were related to disease duration (r = 0.76, P = 0.028), whereas both GH (r = -0.91, P = 0.002) and free T(4) (r = -0.71, P = 0.050) levels correlated inversely with body fat content. Apart from a mild increase in free T(4) levels, we found no indications for altered somatotrophic, thyrotrophic and lactotrophic axes activity in early-stage PD patients.

  20. Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born.

    Science.gov (United States)

    Schweizer, Michael T; Antonarakis, Emmanuel S

    2012-08-01

    The number of life-prolonging therapies proven effective in the treatment of metastatic castrate-resistant prostate cancer (CRPC) has been limited until recently. In the past 2 years several such therapies have come to market. In 2010, the autologous immunotherapy sipuleucel-T and the next-generation taxane cabazitaxel were approved in this setting. However, abundant evidence has shown that CRPC growth continues to be driven through androgen-dependent signaling. Both of these drugs fail to take advantage of this targetable oncogenic pathway. Potent specific inhibitors of cytochrome P450-17 have been engineered with the aim of suppressing androgen synthesis beyond that seen with the luteinizing hormone-releasing hormone agonists/antagonists. Abiraterone acetate was developed by rational design based on a pregnenolone parent structure. Its approval by the US Food and Drug Administration (FDA) was granted in 2011 based on phase III data demonstrating an overall survival advantage compared with placebo. More recently, other drugs that act along the androgen signaling pathway, such as orteronel (TAK-700), galeterone (TOK-001), enzalutamide (MDV3100) and ARN-509, have shown promise in clinical trials. Some of these are expected to gain FDA approval in the near future. Here, we review abiraterone and other novel androgen-directed therapeutic strategies for the management of advanced prostate cancer.

  1. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation.

    Science.gov (United States)

    Hu, Rui; Wang, Zhisheng; Peng, Quanhui; Zou, Huawei; Wang, Hongze; Yu, Xiaoqiang; Jing, Xiaoping; Wang, Yixin; Cao, Binghai; Bao, Shanke; Zhang, Wenhua; Zhao, Suonan; Ji, Hanzhong; Kong, Xiangying; Niu, Quanxi

    2016-01-01

    The objective of this study was to investigate the effects of growth hormone-releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38-83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P growth retardation (average body weight 54.8 ± 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 ± 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P muscle (Pmuscle (P muscle (Pmuscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP-2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway.

  2. Sex Hormones and Tendon

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2016-01-01

    The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood....... The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet...... has also been linked to a reduced responsiveness to relaxin. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens....

  3. Hormones in pregnancy

    Directory of Open Access Journals (Sweden)

    Pratap Kumar

    2012-01-01

    Full Text Available The endocrinology of human pregnancy involves endocrine and metabolic changes that result from physiological alterations at the boundary between mother and fetus. Progesterone and oestrogen have a great role along with other hormones. The controversies of use of progestogen and others are discussed in this chapter. Progesterone has been shown to stimulate the secretion of Th2 and reduces the secretion of Th1 cytokines which maintains pregnancy. Supportive care in early pregnancy is associated with a significant beneficial effect on pregnancy outcome. Prophylactic hormonal supplementation can be recommended for all assisted reproduction techniques cycles. Preterm labor can be prevented by the use of progestogen. The route of administration plays an important role in the drug′s safety and efficacy profile in different trimesters of pregnancy. Thyroid disorders have a great impact on pregnancy outcome and needs to be monitored and treated accordingly. Method of locating review: Pubmed, scopus

  4. Biosimilar growth hormone.

    Science.gov (United States)

    Saenger, Paul

    2012-01-01

    As the first wave of biopharmaceuticals is expiring, biosimilars or follow-on -protein products (FOPP's) have emerged. Biosimilar drugs are cheaper than the originator/comparator drug. The regulatory foundation for these products is more advanced and better codified in Europe than in the US. Biosimilar soamtropin has been approved in both the US and Europe. The scientific viability of biosimilar drugs and especially growth hormone has been proven by several rigorously conducted clinical trials. Efficacy and safety data (growth rates, IGF-1 generation) for up to 7 y for pediatric indications measure up favorably to previously approved growth hormones which served as reference comparators. The Obama Administration appears to be committed to establish innovative pathways for the approval of biologics and biosimilars in the US. The cost savings in health care expenditures will be substantial as the global sales of biologics have reached $ 93 billion in 2009.

  5. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes......, paracrine, spermiocrine secretion etc.), so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor, or a fertility factor. The molecular targets of each bioactive peptide are specific G-protein coupled receptors expressed in the cell membranes of different target cells...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization...

  6. The wound hormone jasmonate

    OpenAIRE

    Koo, Abraham J. K.; Howe, Gregg A.

    2009-01-01

    Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic...

  7. Growth Hormone and Aging

    Science.gov (United States)

    2000-08-01

    thru ADP010582 UNCLASSIFIED 23-1 GROWTH HORMONE AND AGING J.A.F. Tresguerres , Perez Romero, N. de las Heras, S. Vazquez, C. Ariznavarreta Complutense... Tresguerres 1996). GHRH is were treated as children with GH, a significant secreted in peaks as well as somatostatin, both number of problems were detected...of GH ( Tresguerres 1996) reduction in muscular and bone mass together IGFI is a peptide of 70 aminoacids that shows with an increase in body fat

  8. [Acne and hormones].

    Science.gov (United States)

    Faure, Michel

    2002-04-15

    Androgens stimulate sebum production which is necessary for the development of acne. Acne in women may thus be considered as a manifestation of cutaneous androgenization. Most of acnes may be related to an idiopathic skin hyperandrogenism due to in situ enzyme activity and androgen receptor hypersensitivity, as also noted in idiopathic hirsutism. Some acne may correspond to elevated ovarian or adrenal androgen secretion. The presence of acne in women may lead to a diagnosis of functional hyperandrogenism, either polycysticovary syndrome or nonclassical 21-hydroxylase deficiency. Plasma level assays for testosterone, delta 4 androstenedione and 17-OH progesterone and ovarian echography are necessary to determine the possibility for an ovarian or adrenal hyperandrogenism, but not to better treat acne. The goal of hormonal therapy in acne is to oppose the effects of androgens on the sebaceous gland. Hormones may be used in female acne in the absence of endocrine abnormalities. Antiandrogens (cyproterone acetate or aldactone) may be useful in severe acne, hormonal contraceptives with cyproterone acetate or non androgenic progestins in mild or common acne often in association with other anti-acneic drugs. Glucocorticoids have to be administered in acne fulminans and other forms of acute, severe, inflammatory acne, for their anti-inflammatory properties.

  9. [Hormones and the cardiovascular system].

    Science.gov (United States)

    Lacka, Katarzyna; Czyzyk, Adam

    2008-01-01

    Hormones have an influence on many tissues and organs, including the cardio-vascular system (CVS). Depending on their activity on CVS, they can be divided into 4 groups: having hypertensive or hypotensive influence and chronotropic positive or negative action. Endocrine regulation in CVS may occur in many ways. Apart from hormones usually connected with CVS regulation, other more recently, discovered ones can act on it. A few of these act directly through specific receptors in heart or vessel wall cells, whereas some act indirectly - stimulating other neuroendocrine factors. Additionally, novel mechanisms of signal transduction have been discovered for steroid and thyroid hormones, which are independent of gene transcription regulation and are - known as "nongenomic". Hormones which increase blood pressure include: urotensin II, endothelins, angiotensin II, catecholamines, aldosterone, antidiuretic hormone, glucocorticosteroids, thyroid hormones, growth hormone and leptin. On the other hand, blood pressure can be decreased by: natriuretic peptides, the calcitonin gene-related peptide (CGRP) family, angiotensin 1-7, substance P, neurokinin A, ghrelin, Parathyroid hormone-related protein (PTHrP), oxytocin, and, sex hormones. Hormones which when appearing in excess increase the heart rate are: catecholamines, endothelins, glucocorticosteroids, thyroid hormones, leptin and PTHrP. Those which decrease the heart rate include: natriuretic peptides, substance P, neurokinin A, oxytocin, angiotensin 1-7. This paper describes the contemporary view of the functions of hormones which act on the vessel tree and heart. The particular effect of mediator depends on many circumstances i.e.: hormone concentration, receptor type. It may also undergo contraregulation. The majority of those hormones play an important role in the pathogenesis of CVS diseases', which can result in the development of new medicines.

  10. Application of ovine luteinizing hormone (LH) radioimmunoassay in the quantitation of LH in different mammalian species. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Millar, R.P.; Aehnelt, C.

    1977-09-01

    A sensitive double antibody radioimmunoassay has been developed for measuring luteinizing hormone (LH) in various African mammalian species, using rabbit anti-ovine LH serum (GDN 15) and radioiodinated rat LH or ovine LH. Serum and pituitary homogenates from some African mammals (hyrax, reedbuck, sable, impala, tsessebe, thar, spring-hare, ground squirrel and cheetah, as well as the domestic sheep, cow and horse and laboratory rat and hamster) produced displacement curves parallel to that of the ovine LH standards. The specificity of the assay was examined in detail for one species, the rock hyrax. Radioimmunoassay and bioassay estimates of LH in hyrax pituitaries containing widely differing quantities of pituitary hormones were similar. In sexually active male hyrax mean plasma LH was 12.1 ng/ml and pituitary LH 194 ..mu..g/gland, but in sexually quiescent hyrax mean plasma LH was 2.4 ng/ml and mean pituitary LH 76 ..mu..g/gland. Intravenous injection of 10 ..mu..g of luteinizing hormone releasing hormone increased mean LH levels in hyrax from 0.9 ng/ml to 23.2 ng/ml by 30 min. Conversely, im injection of 250 ..mu..g testosterone induced a fall in LH levels in male hyrax from 1.7 ng/ml to 0.7 ng/ml 6 h after administration. Although the specificity of the assay for quantitating plasma LH in other species was not categorically established, there was a good correlation between plasma LH concentration and reproductive state in the bontebok, impala, spring-hare, thar, cheetah, domestic horse and laboratory rat, suggesting the potential use of the antiserum in quantitating LH in a variety of mammalian species.

  11. Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Charlotte Guyader

    Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

  12. Growth hormone and aging

    OpenAIRE

    Bartke, Andrzej; Brown-Borg, Holly; Kinney, Beth; Mattison, Julie; Wright, Chris; Hauck, Steven; Coschigano, Karen; Kopchick, John

    2000-01-01

    The potential usefulness of growth hormone (GH) as an anti-aging therapy is of considerable current interest. Secretion of GH normally declines during aging and administration of GH can reverse age-related changes in body composition. However, mutant dwarf mice with congenital GH deficiency and GH resistant GH-R-KO mice live much longer than their normal siblings, while a pathological elevation of GH levels reduces life expectancy in both mice and men. We propose that the actions of GH on gro...

  13. Cost-efficacy analysis of hormonal treatments for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Sergio Iannazzo

    2008-09-01

    Full Text Available Introduction: prostatic cancer is the second more frequent cancer in Italy (after lung cancer and is the third cancer-related death cause. Age is the principal risk factor and, given the ageing process undergoing in the Italian population, it seems clear that the public sanitary expenditure to treat the disease is bound to increase, arising the need to perform pharmacoeconomic evaluations of the therapeutic strategies available. Methods: we performed a cost/utility analysis, through a Markov model, of several hormonal therapies in patients with advanced prostate cancer who underwent radical prostatectomy, from the biochemical recurrence to death. Nine androgen suppression therapies were considered: orchiectomy, two nonsteroidal antiandrogens (NSAA, four luteinizing hormone-releasing hormone (LHRH agonists, cyproterone acetate and the association of a NSAA and a LHRH (BAT. In the simulation the androgen suppression therapies were started at the PSA recurrence and never stopped until death. The model used the Italian NHS prospective and a time horizon corresponding to patient’s lifetime. Drug costs were calculated for each therapy, considering the less costly brand. Results: all the considered therapies produced a life expectancy (LE of about 12 life years (LYs with a small variability ranging from 12.3 LYs for BAT (the most effective to 11.37 LYs for NSAA-flutamide (the least effective. Quality adjusted life expectancy ranged from 9.98 QALYs for BAT to 9.28 QALYs for NSAA-flutamide. The average cost per patient presented a more enhanced variability, from 12,538 Euro for orchiectomy to 59,496 Euro for NSAA-bicalutamide. Among all the alternatives orchiectomy resulted the most cost/effective alternative with a cost/utility ratio of about 1,300 Euro/QALY. In the LHRH-agonists class leuprorelin was the most cost/effective with about 2,200 Euro/QALY. A one-way sensitivity analysis showed a substantial stability of the results. Conclusions: BAT

  14. Growth hormone, ghrelin and peptide YY secretion after oral glucose administration in healthy and obese women.

    Science.gov (United States)

    Outeiriño-Blanco, E; Garcia-Buela, J; Sangiao-Alvarellos, S; Pertega-Diaz, S; Martinez-Ramonde, T; Cordido, F

    2011-07-01

    The mechanism of the altered GH secretion in obesity is unclear. There is evidence that oral glucose (OG) administration initially decreases and subsequently stimulates GH secretion. Ghrelin is a peptide that displays strong growth hormone-releasing activity. Its physiological importance on GH regulation is unclear. Our aim was to study fasting GH concentrations and their response to OG administration in relation with ghrelin secretion in obese and healthy women, in order to elucidate the hypothetical participation of ghrelin on post-oral glucose GH secretion. 36 women were included in the study. After an overnight fast, 75 g of oral glucose was administered; glucose, insulin, ghrelin, and PYY (1-36) were obtained at baseline and during 300 min. The area under the curve between 0 and 300 min (AUC) of GH μ/l·min) was lower in obese patients than in controls; 262.5±57.5 vs. 534.9±95.6, p=0.01, for obese and controls respectively. GH peak (μg/l) was lower in obese patients than in controls; 3.7±0.7 vs. 7.1±1.0, p=0.012, for obese and controls, respectively. The AUC of total ghrelin (pg/ml·min) was lower in obese patients than in controls; 233,032±12,641 vs. 333,697±29,877, p=0.004, for the obese patients and controls respectively. PYY (1-36) was similar in obese and healthy women after OG. There were significant correlations between the different indices of post-oral glucose GH and ghrelin secretion. These data suggest that ghrelin is a physiological regulator of GH in the post-oral glucose state, and the decreased ghrelin secretion could be one of the mechanisms responsible for the altered GH secretion in obesity.

  15. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    Science.gov (United States)

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  16. Sex Hormones and Ischemic Stroke

    DEFF Research Database (Denmark)

    Holmegard, Haya N; Nordestgaard, Børge G; Jensen, Gorm B

    2016-01-01

    CONTEXT AND OBJECTIVE: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. DESIGN, SETTING, AND PARTICIPANTS: Adult men (n...

  17. Hormonal Programming Across the Lifespan

    Science.gov (United States)

    Tobet, Stuart A; Lara, Hernan E; Lucion, Aldo B; Wilson, Melinda E; Recabarren, Sergio E; Paredes, Alfonso H

    2013-01-01

    Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function. PMID:22700441

  18. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  19. Hormone therapy for transgender patients

    Science.gov (United States)

    2016-01-01

    Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219

  20. Leptin: a multifunctional hormone

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility, and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin's activities in vivo may have potential therapeutic benefits.

  1. Types of Cancer Treatment: Hormone Therapy

    Science.gov (United States)

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  2. Hormonal programming across the lifespan.

    Science.gov (United States)

    Nugent, B M; Tobet, S A; Lara, H E; Lucion, A B; Wilson, M E; Recabarren, S E; Paredes, A H

    2012-07-01

    Hormones influence countless biological processes across an animal's lifespan. Many hormone-mediated events occur within developmental sensitive periods, during which hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous selective critical periods in development with different targets being affected during different periods. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal steroid hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of critical hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be an important mediator of sexual differentiation of the neonatal brain. Brain targets of hormonal programming, such as the paraventricular nucleus of the hypothalamus, may be critical in influencing the development of peripheral targets, such as the ovary. Exposure to excess hormones can cause abnormalities in the ovary during development leading to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased activity of the sympathetic nerve and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function.

  3. Impact of the Leu7Pro polymorphism of preproNPY on diurnal NPY and hormone secretion in type 2 diabetes.

    Science.gov (United States)

    Jaakkola, U; Koulu, M; Karvonen, M K; Seppälä, H; Pesonen, U; Vahlberg, T; Kallio, J

    2007-05-01

    Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g. circulation, hormone release and angiogenesis. Earlier studies have shown that the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with increased risk for vascular complications in type 2 diabetes. The mechanism for this maybe altered transmitter and hormone levels or altered cardiovascular functions, which have been observed in healthy subjects having the Leu7Pro polymorphism. The current study was undertaken to explore if the Leu7Pro polymorphism has an impact on these functions in subjects with type 2 diabetes. Diurnal measurements were performed for Finnish Caucasian type 2 diabetes patients of two preproNPY genotypes (matched by sex, age, BMI, duration of diabetes and HbA1c) in resting position to prevent sympathetic stimulation. Standard meals were offered during the 24-hour study period. Nine subjects with the Leu7Pro polymorphism and ten subjects without this polymorphism were studied. Plasma concentrations of NPY, glucose, insulin, cortisol, prolactin and leptin were measured by taking blood samples at 20 time points (from 8 a.m. to 8 a.m.). Heart rate and blood pressure were measured at the same time points. The results show that NPY concentrations were similar in both preproNPY genotypes. Glucose, insulin, cortisol and leptin concentrations as well as heart rate and blood pressure were also similar. However, a significant difference between genotypes was found in the association of NPY concentrations with cortisol concentrations (p for difference=0.002). Also a statistically significant negative association of plasma NPY levels with plasma glucose levels was found in both genotypes. Since no impact of preproNPY genotype on mean NPY or hormone levels were detected in subjects with type 2 diabetes, the mechanisms for the increased risk for diabetic complications in the subjects with the Leu7Pro polymorphism need to be further explored.

  4. Thyroid hormones and cardiovascular disease.

    Science.gov (United States)

    Jabbar, Avais; Pingitore, Alessandro; Pearce, Simon H S; Zaman, Azfar; Iervasi, Giorgio; Razvi, Salman

    2017-01-01

    Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.

  5. Biological effects of thyroid hormones

    Directory of Open Access Journals (Sweden)

    T. S. Saatov

    2013-12-01

    Full Text Available The article presents the findings from the study on multifunctional effects of thyroid hormones in relation to normal and malignantly transformed tissues and cells. Both “rapid” and «slow» effects of thyroid hormones including calorigenic effects and effects over adenylate cyclase – cAMP system have been described. Thyroxin (Т4 has been established capable to inhibit proliferation and to induce apoptosis of cells carrying Т4 receptors on their membranes as well as to change course of metabolic processes under its effect. Spectrum of Т4 targets is quite broad to include not only cells of hormone-producing organs, to name those of the breast and the colon, but also other types of cells to name melanin-containing ones; Т4 effects resulting in reconstruction of presentation of regulatory proteins on the cell membrane surface to ultimately activate the process of cell apoptosis. Our findings help determine alternative paths for hormonal regulation of cell proliferation and apoptosis of cells of hormone-dependent tumors, breast cancer, in particular, upon impossibility to regulate the processes by conventional methods. This facilitates understanding mechanisms for activation of signal system of the breast cancer’s cells by hormones upon changes in expression of receptors on the cells’ surface, making possible development of novel strategy for replacement therapy of hormone-dependent tumors upon low efficacy of drug therapy.

  6. Genotoxic potential of nonsteroidal hormones

    Directory of Open Access Journals (Sweden)

    Topalović Dijana

    2015-01-01

    Full Text Available Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non­steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress. [Projekat Ministarstva nauke Republike

  7. NCBI nr-aa BLAST: CBRC-DNOV-01-2844 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2844 gb|AAI20749.1| Growth hormone releasing hormone receptor [Mus musculus] gb|AAI20775.1| Gro...wth hormone releasing hormone receptor [Mus musculus] AAI20749.1 1e-114 53% ...

  8. NCBI nr-aa BLAST: CBRC-MMUS-06-0057 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUS-06-0057 gb|AAI20749.1| Growth hormone releasing hormone receptor [Mus musculus] gb|AAI20775.1| Gro...wth hormone releasing hormone receptor [Mus musculus] AAI20749.1 0.0 100% ...

  9. NCBI nr-aa BLAST: CBRC-RNOR-04-0139 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-04-0139 gb|AAI20749.1| Growth hormone releasing hormone receptor [Mus musculus] gb|AAI20775.1| Gro...wth hormone releasing hormone receptor [Mus musculus] AAI20749.1 0.0 85% ...

  10. NCBI nr-aa BLAST: CBRC-PVAM-01-1440 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PVAM-01-1440 ref|NP_851363.1| growth hormone releasing hormone receptor [Bos t...aurus] dbj|BAA84960.1| growth hormone-releasing hormone receptor long form [Bos taurus] NP_851363.1 1e-148 72% ...

  11. NCBI nr-aa BLAST: CBRC-FRUB-02-0788 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FRUB-02-0788 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-120 52% ...

  12. NCBI nr-aa BLAST: CBRC-CPOR-01-2037 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CPOR-01-2037 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 1e-110 72% ...

  13. NCBI nr-aa BLAST: CBRC-PCAP-01-0323 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PCAP-01-0323 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor [Rattus norvegicus] NP_036982.1 1e-159 65% ...

  14. NCBI nr-aa BLAST: CBRC-XTRO-01-0270 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-0270 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-07 34% ...

  15. NCBI nr-aa BLAST: CBRC-RNOR-04-0139 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-04-0139 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 0.0 91% ...

  16. NCBI nr-aa BLAST: CBRC-MLUC-01-0263 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0263 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor [Rattus norvegicus] NP_036982.1 1e-119 53% ...

  17. NCBI nr-aa BLAST: CBRC-MEUG-01-1979 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1979 ref|NP_001009454.1| growth hormone releasing hormone receptor [Ov...is aries] gb|AAG29239.1| pituitary growth hormone releasing hormone receptor [Ovis aries] NP_001009454.1 1e-133 60% ...

  18. NCBI nr-aa BLAST: CBRC-TNIG-22-0056 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TNIG-22-0056 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-117 54% ...

  19. NCBI nr-aa BLAST: CBRC-MDOM-11-0021 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-11-0021 ref|NP_851363.1| growth hormone releasing hormone receptor [Bos t...aurus] dbj|BAA84960.1| growth hormone-releasing hormone receptor long form [Bos taurus] NP_851363.1 1e-127 59% ...

  20. NCBI nr-aa BLAST: CBRC-TTRU-01-1314 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-1314 ref|NP_851363.1| growth hormone releasing hormone receptor [Bos t...aurus] dbj|BAA84960.1| growth hormone-releasing hormone receptor long form [Bos taurus] NP_851363.1 0.0 90% ...

  1. NCBI nr-aa BLAST: CBRC-OCUN-01-0178 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OCUN-01-0178 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 6e-49 51% ...

  2. NCBI nr-aa BLAST: CBRC-OLAT-04-0017 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-04-0017 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-122 54% ...

  3. NCBI nr-aa BLAST: CBRC-OGAR-01-0206 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OGAR-01-0206 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 8e-59 61% ...

  4. NCBI nr-aa BLAST: CBRC-TGUT-37-0033 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-37-0033 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 1e-107 60% ...

  5. NCBI nr-aa BLAST: CBRC-XTRO-01-2986 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-2986 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-139 70% ...

  6. NCBI nr-aa BLAST: CBRC-FRUB-02-0296 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FRUB-02-0296 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-119 54% ...

  7. NCBI nr-aa BLAST: CBRC-OLAT-17-0030 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-17-0030 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-113 52% ...

  8. NCBI nr-aa BLAST: CBRC-LAFR-01-0274 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-LAFR-01-0274 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 1e-106 85% ...

  9. NCBI nr-aa BLAST: CBRC-PTRO-08-0019 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-08-0019 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 1e-149 79% ...

  10. NCBI nr-aa BLAST: CBRC-BTAU-01-2615 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-2615 ref|NP_851363.1| growth hormone releasing hormone receptor [Bos t...aurus] dbj|BAA84960.1| growth hormone-releasing hormone receptor long form [Bos taurus] NP_851363.1 0.0 94% ...

  11. NCBI nr-aa BLAST: CBRC-BTAU-01-2615 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-2615 ref|NP_001009454.1| growth hormone releasing hormone receptor [Ov...is aries] gb|AAG29239.1| pituitary growth hormone releasing hormone receptor; GRF receptor; GHRF receptor [Ovis aries] NP_001009454.1 0.0 91% ...

  12. NCBI nr-aa BLAST: CBRC-RMAC-03-0036 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RMAC-03-0036 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 1e-131 67% ...

  13. NCBI nr-aa BLAST: CBRC-MMUS-06-0057 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUS-06-0057 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 0.0 94% ...

  14. NCBI nr-aa BLAST: CBRC-OLAT-04-0021 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-04-0021 ref|NP_001075951.1| growth hormone-releasing hormone receptor [Da...nio rerio] gb|ABJ55981.1| growth hormone-releasing hormone receptor [Danio rerio] NP_001075951.1 1e-160 75% ...

  15. NCBI nr-aa BLAST: CBRC-TNIG-22-0103 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TNIG-22-0103 ref|NP_001075951.1| growth hormone-releasing hormone receptor [Da...nio rerio] gb|ABJ55981.1| growth hormone-releasing hormone receptor [Danio rerio] NP_001075951.1 1e-170 71% ...

  16. NCBI nr-aa BLAST: CBRC-DRER-12-0072 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-12-0072 ref|NP_001075951.1| growth hormone-releasing hormone receptor [Da...nio rerio] gb|ABJ55981.1| growth hormone-releasing hormone receptor [Danio rerio] NP_001075951.1 0.0 99% ...

  17. NCBI nr-aa BLAST: CBRC-GACU-03-0025 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GACU-03-0025 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-113 51% ...

  18. NCBI nr-aa BLAST: CBRC-MDOM-11-0021 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-11-0021 ref|NP_001009454.1| growth hormone releasing hormone receptor [Ov...is aries] gb|AAG29239.1| pituitary growth hormone releasing hormone receptor [Ovis aries] NP_001009454.1 1e-128 60% ...

  19. NCBI nr-aa BLAST: CBRC-GGAL-27-0002 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-27-0002 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 0.0 99% ...

  20. NCBI nr-aa BLAST: CBRC-FRUB-02-0138 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FRUB-02-0138 ref|NP_001075951.1| growth hormone-releasing hormone receptor [Da...nio rerio] gb|ABJ55981.1| growth hormone-releasing hormone receptor [Danio rerio] NP_001075951.1 1e-173 72% ...

  1. NCBI nr-aa BLAST: CBRC-OCUN-01-0178 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OCUN-01-0178 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 7e-66 48% ...

  2. NCBI nr-aa BLAST: CBRC-DRER-12-0013 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-12-0013 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-114 50% ...

  3. NCBI nr-aa BLAST: CBRC-DNOV-01-2844 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2844 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor NP_036982.1 1e-116 53% ...

  4. NCBI nr-aa BLAST: CBRC-GACU-08-0022 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GACU-08-0022 ref|NP_001075951.1| growth hormone-releasing hormone receptor [Da...nio rerio] gb|ABJ55981.1| growth hormone-releasing hormone receptor [Danio rerio] NP_001075951.1 1e-159 74% ...

  5. NCBI nr-aa BLAST: CBRC-STRI-01-2904 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2904 ref|NP_036982.1| growth hormone releasing hormone receptor [Rattu...s norvegicus] gb|AAA41221.1| growth hormone-releasing hormone receptor [Rattus norvegicus] NP_036982.1 1e-167 77% ...

  6. NCBI nr-aa BLAST: CBRC-ACAR-01-0819 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0819 ref|NP_001098428.1| growth hormone releasing hormone receptor [Ga...llus gallus] gb|ABS00398.1| growth hormone-releasing hormone receptor precursor [Gallus gallus] NP_001098428.1 1e-109 51% ...

  7. NCBI nr-aa BLAST: CBRC-MLUC-01-0263 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0263 ref|NP_851363.1| growth hormone releasing hormone receptor [Bos t...aurus] dbj|BAA84960.1| growth hormone-releasing hormone receptor long form [Bos taurus] NP_851363.1 1e-123 58% ...

  8. NCBI nr-aa BLAST: CBRC-GGOR-01-0759 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGOR-01-0759 ref|NP_001009824.1| growth hormone releasing hormone receptor iso...form b precursor [Homo sapiens] gb|EAW93976.1| growth hormone releasing hormone receptor, isoform CRA_d [Homo sapiens] NP_001009824.1 1e-105 94% ...

  9. Hormonal signaling in the gut.

    Science.gov (United States)

    Côté, Clémence D; Zadeh-Tahmasebi, Melika; Rasmussen, Brittany A; Duca, Frank A; Lam, Tony K T

    2014-04-25

    The gut is anatomically positioned to play a critical role in the regulation of metabolic homeostasis, providing negative feedback via nutrient sensing and local hormonal signaling. Gut hormones, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), are released following a meal and act on local receptors to regulate glycemia via a neuronal gut-brain axis. Additionally, jejunal nutrient sensing and leptin action are demonstrated to suppress glucose production, and both are required for the rapid antidiabetic effect of duodenal jejunal bypass surgery. Strategies aimed at targeting local gut hormonal signaling pathways may prove to be efficacious therapeutic options to improve glucose control in diabetes.

  10. Hormonal Signaling in the Gut*

    Science.gov (United States)

    Côté, Clémence D.; Zadeh-Tahmasebi, Melika; Rasmussen, Brittany A.; Duca, Frank A.; Lam, Tony K. T.

    2014-01-01

    The gut is anatomically positioned to play a critical role in the regulation of metabolic homeostasis, providing negative feedback via nutrient sensing and local hormonal signaling. Gut hormones, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), are released following a meal and act on local receptors to regulate glycemia via a neuronal gut-brain axis. Additionally, jejunal nutrient sensing and leptin action are demonstrated to suppress glucose production, and both are required for the rapid antidiabetic effect of duodenal jejunal bypass surgery. Strategies aimed at targeting local gut hormonal signaling pathways may prove to be efficacious therapeutic options to improve glucose control in diabetes. PMID:24577102

  11. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    , oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses......%. The increased insulin responses after the operation, one of the important mechanisms whereby these operations cause diabetes remission, is clearly due to a combination of the increased glucose absorption rates and the exaggerated GLP-1 secretion. The hormonal changes are therefore very important...

  12. Both radical prostatectomy following treatment with neoadjuvant LHRH agonist and estramustine and radiotherapy following treatment with neoadjuvant hormonal therapy achieved favorable oncological outcome in high-risk prostate cancer: a propensity-score matching analysis.

    Science.gov (United States)

    Koie, Takuya; Ohyama, Chikara; Yamamoto, Hayato; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Yoneyama, Tohru; Tobisawa, Yuki; Aoki, Masahiko; Takai, Yoshihiro

    2014-04-30

    To date, the different treatment modalities for high-risk prostate cancer (Pca) have not been compared in any sufficiently large-scale, prospective, randomized clinical trial. We used propensity-score matching analysis to compare the oncological outcomes of high-risk prostate cancer between patients treated with radical prostatectomy (RP) and those treated with radiation therapy (RT). We studied 216 patients who received neoadjuvant therapy followed by RP (RP cohort) and 81 patients who received neoadjuvant androgen-deprivation therapy (ADT) followed by RT (RT cohort). The RP cohort received a luteinizing hormone-releasing hormone agonist and estramustine phosphate (280 mg/day) for 6 months prior to RP. The RT cohort received ADT for at least 6 months prior to RT using a 3-dimensional conformal radiotherapy technique. The total radiation dose was 70 to 76 Gy administered at 2 Gy/fraction. Propensity-score matching identified 78 matched pairs of patients. The 3-year overall survival rates were 98.3% and 92.1% in the RP and RT groups, respectively (P=0.156). The 3-year biochemical recurrence-free survival rates were 86.4% and 89.4% in the RP and RT groups, respectively (P=0.878). Our study findings may suggest almost identical cancer control of RP and RT with appropriate neoadjuvant therapy in high-risk Pca. Therefore, issues of health-related quality of life may have an important impact on decision making in treatment of high-risk Pca.

  13. Network identification of hormonal regulation.

    Directory of Open Access Journals (Sweden)

    Daniel J Vis

    Full Text Available Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for detecting regulatory relations between hormones. This is demonstrated with a cohort of obese women, who underwent blood sampling at 10 minute intervals for 24-hours. The cohort was treated with bromocriptine in an attempt to clarify how hormone relations change by treatment. The detected regulatory relations are summarized in a network graph and treatment-induced changes in the relations are determined. The proposed method identifies many relations, including well-known ones. Ultimately, the method provides ways to improve the description and understanding of normal hormonal relations and deviations caused by disease or treatment.

  14. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  15. Menopausal Hormone Therapy and Cancer

    Science.gov (United States)

    ... Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  16. Measurement of the incretin hormones

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette;

    2015-01-01

    The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrat......The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma...... concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological...

  17. Organizational Actions of Metabolic Hormones

    OpenAIRE

    Bouret, Sebastien G.

    2013-01-01

    Brain development is a complex and dynamic process, and many environmental factors have been found to influence the normal development of neural pathways. Cumulative evidence suggests that metabolic hormones that regulate the hypothalamic circuits that control energy homeostasis function in much the same way that sex steroids act on sexually dimorphic circuits. For example, although the effects of the adipocyte-derived hormone leptin were originally thought to be limited to the neural control...

  18. Does growth hormone cause cancer?

    OpenAIRE

    Jenkins, P.J.; Mukherjee, A.; Shalet, S. M.

    2006-01-01

    KEYWORDS - CLASSIFICATION: adverse effects;Acromegaly;Adult;Animals;cancer epidemiology;complications;Child;Child Development;Colorectal Neoplasms;deficiency;epidemiology;etiology;Evaluation;Growth Hormone;Human Growth Hormone;Humans;Insulin-Like Growth Factor I;mechanisms of carcinogenesis;Neoplasm Recurrence,Local;Neoplasms;Neoplasms,Multiple Primary;physiology;physiopathology;Risk Factors;secretion;therapy. The ability of GH, via its mediator peptide IGF-1, to influence regulation of ce...

  19. Simple hormones but complex signalling.

    Science.gov (United States)

    Vogler, Hannes; Kuhlemeier, Cris

    2003-02-01

    It has not been easy to make sense of the pleiotropic effects of plant hormones, especially of auxins; but now, it has become possible to study these effects within the framework of what we know about signal transduction in general. Changes in local auxin concentrations, perhaps even actively maintained auxin gradients, signal to networks of transcription factors, which in turn signal to downstream effectors. Transcription factors can also signal back to hormone biosynthetic pathways.

  20. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  1. The evolution of peptide hormones.

    Science.gov (United States)

    Niall, H D

    1982-01-01

    Despite limitations in our present knowledge it is already possible to discern the main features of peptide hormone evolution, since the same mechanisms (and indeed the same hormone molecules) function in many different ways. This underlying unity of organization has its basis in the tendency of biochemical networks, once established, to survive and diversify. The most surprising recent findings in endocrinology have been the discovery of vertebrate peptide hormones in multiple sites within the same organism, and the reports, persuasive but requiring confirmation, of vertebrate hormones in primitive unicellular organisms (20, 20a). Perhaps the major challenge for the future is to define the roles and interactions of the many peptide hormones identified in brain (18). The most primitive bacteria and the human brain, though an enormous evolutionary distance apart, may have more in common than we have recognized until now. As Axelrod & Hamilton have pointed out in a recent provocative article, "The Evolution of Cooperation" (1), bacteria, though lacking a brain, are capable of adaptive behavior that can be analysed in terms of game theory. It is clear that we can learn a great deal about the whole evolutionary process from a study of the versatile and durable peptide hormones molecules.

  2. Natriuretic hormones in brain function

    Directory of Open Access Journals (Sweden)

    David eLichtstein

    2014-11-01

    Full Text Available Natriuretic hormones include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP, the gastrointestinal peptides (guanylin and uroguanylin, and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume and blood pressure. In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of natriuretic hormones is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the natriuretic hormones and their receptors in the brain will be summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that natriuretic hormones participate in the central regulation of blood pressure, neuroprotection, satiety, and various psychiatric conditions, including: anxiety, addiction and depressive disorders. In addition, the interactions between the different natriuretic hormones in the periphery and the brain are discussed.

  3. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  4. Thyroid Hormone Deiodinases and Cancer

    Directory of Open Access Journals (Sweden)

    Antonio eBianco

    2012-06-01

    Full Text Available Deiodinases constitute a group of thioredoxin-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4 to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i they may represent a useful cancer marker and/or (ii could play a role in modulating cell proliferation - in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS-13 cells is 3-4 fold higher. In basal cell carcinoma (BCC cells, sonic hedgehog (Shh-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a 5-fold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches.

  5. Gastrointestinal hormone research - with a Scandinavian annotation

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2015-01-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones...... as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions...... under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated posttranslational...

  6. Effects of cysteamine on mRNA levels of growth hormone and its receptors and growth in orange-spotted grouper (Epinephelus coioides).

    Science.gov (United States)

    Li, Yun; Liu, Xiaochun; Zhang, Yong; Ma, Xilan; Lin, Haoran

    2013-06-01

    Effects of cysteamine (CS) on growth hormone (GH) mRNA, two types of growth hormone receptor (GHR) mRNAs and growth rate in orange-spotted grouper (Epinephelus coioides) were investigated. CS could cause a modification in the structure of somatostatin, which is the most important neuroendocrine inhibitor of basal and stimulated growth hormone synthesis and release, and renders it nonimmunoreactive probably through interaction with the disulfide bonds. In the present study, cysteamine hydrochloride (CSH) enhanced the level of pituitary GH mRNA in a dose-dependent manner through attenuating or deleting the inhibiting action of somatostatin on GH mRNA expression. CSH at relatively low doses (from 1 to 3 mg/g diet) enhanced the levels of two types of GHR mRNAs in dose-dependent manner, whereas the stimulation induced by CSH declined from the peak at higher dose of CSH (4 mg/g diet). It might be attributed to the variation in GH-induced up-regulation of GHRs at different doses of GH. Feeding of CSH could induce remarkable enhancement of growth rate in orange-spotted grouper. In addition, the stimulatory effect of CSH could be potentiated by the additive effect of luteinizing hormone-releasing hormone analog (LHRH-A). Compared with individual treatments, combined feeding of CSH and LHRH-A caused more efficient elevation of growth rate after 8 weeks of feeding. CSH and LHRH-A individually and in combination remarkably increased the levels of GH and GHR mRNAs compared with the control. The combined administration of CSH and LHRH-A in diet was most effective to enhance the level of GH and GHR1 mRNA. The morphological characteristics of the experimental fish were evaluated. Compared with control, the ratios of muscle RNA/DNA, condition factors (CF) and feed conversion efficiency (FCE) were significantly enhanced in the treated groups, while the highest values were observed in the combined treatment. All the results suggested that CSH (1-3 mg/g diet) is an effective

  7. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  8. Electrochemical biosensors for hormone analyses.

    Science.gov (United States)

    Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

    2015-06-15

    Electrochemical biosensors have a unique place in determination of hormones due to simplicity, sensitivity, portability and ease of operation. Unlike chromatographic techniques, electrochemical techniques used do not require pre-treatment. Electrochemical biosensors are based on amperometric, potentiometric, impedimetric, and conductometric principle. Amperometric technique is a commonly used one. Although electrochemical biosensors offer a great selectivity and sensitivity for early clinical analysis, the poor reproducible results, difficult regeneration steps remain primary challenges to the commercialization of these biosensors. This review summarizes electrochemical (amperometric, potentiometric, impedimetric and conductometric) biosensors for hormone detection for the first time in the literature. After a brief description of the hormones, the immobilization steps and analytical performance of these biosensors are summarized. Linear ranges, LODs, reproducibilities, regenerations of developed biosensors are compared. Future outlooks in this area are also discussed.

  9. [Women, immunity and sexual hormones].

    Science.gov (United States)

    Denenberg, R

    1995-01-01

    How a weakened immune system affects the female's reproductive system is explained. The female's endocrine system controls the menstrual and reproductive systems, and the immune system attacks harmful substances and organisms. The hypothalamus stimulates the pituitary gland to produce the hormones FSH and LH, which in turn signal the ovaries to produce estrogen and progesterone. These hormones cause a mature egg to be released. If fertilized, the egg remains within the uterus; if not, menstruation occurs. HIV-positive females often complain of menstrual cycle changes, such as irregular periods, depression, or pain. The virus, other complications, or medications, such as AZT, may cause these symptoms. Estrogen therapy may help those with suppressed immune systems who have premature menopause. Oral contraceptives offer protection against pregnancy, but not HIV. It is not known if the pill reacts adversely with AIDS treatment drugs. Lists are provided showing the pros and cons of oral contraceptives and hormone therapy.

  10. Phenobarbital blockade of the preovulatory luteinizing hormone surge: association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression

    Science.gov (United States)

    Legan, Sandra J.; Donoghue, Kathleen M.; Franklin, Kathleen M.; Duncan, Marilyn J.

    2009-01-01

    The suprachiasmatic nucleus (SCN) controls the timing of the preovulatory luteinizing hormone (LH) surge in laboratory rodents. Barbiturate administration during a critical period on proestrus delays the surge and prolongs the estrous cycle 1 day. Because a nonphotic timing signal (zeitgeber) during the critical period that phase advances activity rhythms can also induce the latter effect, we hypothesized that barbiturates delay the LH surge by phase-advancing its circadian timing signal beyond the critical period. In experiment 1, locomotor rhythms and estrous cycles were monitored in hamsters for 2–3 wk preinjection and postinjection of vehicle or phenobarbital and after transfer to darkness at zeitgeber time (ZT) 6 on proestrus. Phenobarbital delayed estrous cycles in five of seven hamsters, which exhibited phase shifts that averaged twofold greater than those exhibited by vehicle controls or phenobarbital-injected hamsters with normal cycles. Experiment 2 used a similar protocol, but injections were at ZT 5, and blood samples for LH determination were collected from 1200 to 1800 on proestrus and the next day via jugular cannulae inserted the day before proestrus. Phenobarbital delayed the LH surge 1 day in all six hamsters, but it occurred at an earlier circadian time, supporting the above hypothesis. Experiment 3 investigated whether phenobarbital, like other nonphotic zeitgebers, suppresses SCN Period1 and Period2 transcription. Two hours postinjection, phenobarbital decreased SCN expression of only Period1 mRNA, as determined by in situ hybridization. These results suggest that phenobarbital advances the SCN pacemaker, governing activity rhythms and hormone release in part by decreasing its Period1 gene expression. PMID:19297538

  11. Hormones and prostate cancer: what's next?

    Science.gov (United States)

    Hsing, A W

    2001-01-01

    In summary, the hormonal hypothesis remains one of the most important hypotheses in prostate cancer etiology. Although epidemiologic data regarding the role of hormones are still inconclusive, there are many intriguing leads. Armed with more complete methodological data, state-of-the-art hormone assays, sound epidemiologic design, and a more thorough analytical approach, a new generation of studies should yield critical data and insights to help clarify further the role of hormones in prostate cancer. These new studies may determine ultimately whether racial/ethnic differences in hormonal levels and in genetic susceptibility to hormone-metabolizing genes can help explain the very large racial/ethnic differences in prostate cancer risk.

  12. Advances in male hormonal contraception

    Directory of Open Access Journals (Sweden)

    Costantino Antonietta

    2014-01-01

    Full Text Available Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.

  13. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pParathyroid hormone may be associated with cognitive performance.

  14. Hormonal contraceptives and venous thrombosis

    NARCIS (Netherlands)

    Stegeman, Berendina Hendrika (Bernardine)

    2013-01-01

    Oral contraceptive use is associated with venous thrombosis. However, the mechanism behind this remains unclear. The aim of this thesis was to evaluate genetic variation in the first-pass metabolism of contraceptives, to identify the clinical implications of hormonal contraceptive use after a

  15. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  16. Parathyroid Hormone in Osteoporosis Treatment

    Directory of Open Access Journals (Sweden)

    İ. Özkul

    2002-03-01

    Full Text Available Parathyroid hormone stimulates bone formation, prevents or reverses bone loss, increases bone mass, bone strength and provides protection against fractures. PTH treatment for postmenopausal, male and glucocorticoid- induced osteoporosis proved to be effective in a number of RCTs.

  17. Anabolic steroids and growth hormone.

    Science.gov (United States)

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  18. Hormone receptors in breast cancer

    NARCIS (Netherlands)

    Suijkerbuijk, K. P M; van der Wall, E.; van Diest, P. J.

    2016-01-01

    Steroid hormone receptors are critical for the growth and development of breast tissue as well as of breast cancer. The importance of the role estrogens in breast cancer has been delineated for more than 100 years. The analysis of its expression has been used not only to classify breast cancers but

  19. Hypothalamic effects of thyroid hormone

    NARCIS (Netherlands)

    Zhang, Z.; Boelen, Anita; Bisschop, Peter H; Kalsbeek, A.; Fliers, Eric

    Thyroid hormone (TH) is a key driver of metabolism in mammals. Plasma concentrations of TH are kept within a narrow range by negative feedback regulation in the hypothalamus-pituitary-thyroid (HPT) axis. Plasma TH concentrations are an important determinant of metabolic processes in liver and brown

  20. Hormonal contraceptives and venous thrombosis

    NARCIS (Netherlands)

    Stegeman, Berendina Hendrika (Bernardine)

    2013-01-01

    Oral contraceptive use is associated with venous thrombosis. However, the mechanism behind this remains unclear. The aim of this thesis was to evaluate genetic variation in the first-pass metabolism of contraceptives, to identify the clinical implications of hormonal contraceptive use after a thromb

  1. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pself-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  2. Hormonal determinants of pubertal growth.

    NARCIS (Netherlands)

    Delamarre-van Waal, H.A.; Coeverden, S.C. van; Rotteveel, J.J.

    2001-01-01

    Pubertal growth results from increased sex steroid and growth hormone (GH) secretion. Estrogens appear to play an important role in the regulation of pubertal growth in both girls and boys. In girls, however, estrogens cannot be the only sex steroids responsible for pubertal growth, as exogenous est

  3. Hormonal crosstalk in plant immunity

    NARCIS (Netherlands)

    van der Does, A.

    2012-01-01

    The plant hormones salicylic acid (SA), also known as plant aspirin, and jasmonic acid (JA) play major roles in the regulation of the plant immune system. In general, SA is important for defense against pathogens with a biotrophic lifestyle, whereas JA is essential for defense against insect herbivo

  4. Growth Hormone: Use and Abuse

    Science.gov (United States)

    ... GH helps children grow taller (also called linear growth), increases muscle mass, and decreases body fat. In both children ... syndrome In adults, GH is used to treat • Growth hormone deficiency • Muscle wasting (loss of muscle tissue) from HIV • Short ...

  5. Parathyroid hormone-related protein blood test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003691.htm Parathyroid hormone-related protein blood test To use the ... features on this page, please enable JavaScript. The parathyroid hormone-related protein (PTH-RP) test measures the ...

  6. The 'Love Hormone' May Quiet Tinnitus

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_161110.html The 'Love Hormone' May Quiet Tinnitus Small, preliminary study suggests oxytocin ... tinnitus -- may find some relief by spraying the hormone oxytocin in their nose, a small initial study ...

  7. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ... in my area? Other Names for This Condition dwarfism, growth hormone deficiency dwarfism, pituitary growth hormone deficiency ...

  8. Chelating peptide-immobilized metal ion affinity chromatography. A new concept in affinity chromatography for recombinant proteins.

    Science.gov (United States)

    Smith, M C; Furman, T C; Ingolia, T D; Pidgeon, C

    1988-05-25

    We report our experimental results supporting the hypothesis that a specific metal-chelating peptide (CP) on the NH2 terminus of a protein can be used to purify that protein using immobilized metal ion affinity chromatography (IMAC). The potential utility of this approach resides with recombinant proteins since the nucleotide sequence that codes for the protein can be extended to include codons for the chelating peptide and thereby generate the gene for a chimeric CP-protein that can be cloned, expressed, and affinity-purified with immobilized metal ions. The chelating peptide purification handle could then be removed chemically or enzymatically after purification has been achieved to generate a protein with the natural amino acid sequence. The feasibility of using a chelating peptide as a purification handle has been demonstrated using a leuteinizing hormone-releasing hormone (LHRH) analog, 2-10 LHRH, which contains the previously identified chelating peptide, His-Trp, on the NH2 terminus. 2-10 LHRH had a high affinity for a Ni(II) IMAC column due to the NH2-terminal dipeptide sequence His-Trp, forming a coordination complex with Ni(II), whereas the controls, 3-10 LHRH and 4-10 LHRH, lacking the CP sequence, did not bind. Furthermore, 2-10 LHRH could be purified from a mixture of histidine-containing peptides on a Ni(II) IMAC column in one step. His-Trp proinsulin was used as a model of a recombinant CP-protein. The S-sulfonates of His-Trp-proinsulin and proinsulin were isolated from Escherichia coli engineered to overproduce these proteins as trpLE' fusion proteins. His-Trp-proinsulin(SSO3-)6 had a higher affinity for immobilized Ni(II) than proinsulin (SSO3-)6. Both proteins were eluted by decreasing the pH or by introducing a displacing ligand into the buffer. Ni(II) eluted from the column with much higher concentrations of displacing ligand than the proteins.

  9. Peptide Hormones in the Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  10. "Sex Hormones" in Secondary School Biology Textbooks

    Science.gov (United States)

    Nehm, Ross H.; Young, Rebecca

    2008-01-01

    This study explores the extent to which the term "sex hormone" is used in science textbooks, and whether the use of the term "sex hormone" is associated with pre-empirical concepts of sex dualism, in particular the misconceptions that these so-called "sex hormones" are sex specific and restricted to sex-related physiological functioning. We found…

  11. Hormonal regulation of spermatogenesis in zebrafish

    NARCIS (Netherlands)

    de Waal, P.P.

    2009-01-01

    Across vertebrates, spermatogenesis is under the endocrine control of two hormones, follicle-stimulating hormone (FSH) and androgens; the testicular production and secretion of the latter are controlled by luteinizing hormone. In fish, also the strong steroidogenic potency of Fsh should be taken int

  12. Reproductive Hormones and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2010-12-01

    Full Text Available During the menstrual cycle, pregnancy and breast-feeding periods, as well as in menopausal and post-menopausal periods, the physiological and psychological processes that change according to the hormonal fluctuations influence every women similarly and each one differently. These physiological processes are controlled by neuroendocrine sequences, of which the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis are the most important ones. The hypothalamo-pituitary-gonadal axis affects mood, anxiety, cognition and pain. The interaction of these hormones with mood and behavior is bidirectional. The differences in phenomenology and epidemiology of mood disorders with regards to gender can be explained with the effects of hormones. All of the periods mentioned above are related with mood disorders at terms of risk factors, disease symptoms, progress of disease and response to treatment. Epidemiologic data supports the relationship between the mood disorders and reproductive processes. The prevalence of major depression increases in women with the menarche and ceases in post- menopausal period. Similarly, the initial symptoms of bipolar disorder begins around the menarche period in 50% of the cases. Despite proper treatment, some female patients with major depression experience recurrence during the premenstrual period of their menstrual cycles. The conformity and change in a woman’s brain during pregnancy is controlled dominantly by the neuroendocrine systems, while it is controlled by the external stimuli actively related to the baby during nursing period. The changes that occur are closely related to postpartum mood disorders. Again, all the changes and suspension of medication during this procedure are risk factors for early depressive and dysphoric situations. Variables of a wide range, from follicle stimulating hormone, melatonin, and sleep to body mass index interact with mood disorders in menopausal and post

  13. Cloning of growth hormone, somatolactin, and their receptor mRNAs, their expression in organs, during development, and on salinity stress in the hermaphroditic fish, Kryptolebias marmoratus.

    Science.gov (United States)

    Rhee, Jae-Sung; Kim, Bo-Mi; Seo, Jung Soo; Kim, Il-Chan; Lee, Young-Mi; Lee, Jae-Seong

    2012-04-01

    Salinity is an important parameter that affects survival and metabolism in fish. In fish, pituitary growth hormone (GH) regulates physiological functions including adaptation to different salinity as well as somatic growth. GH is stimulated by growth hormone-releasing hormone (GHRH) and exerts its function via binding to growth hormone receptor (GHR). As Kryptolebias marmoratus is a euryhaline fish, this species would be a useful model species for studying the adaptation to osmotic stress conditions. Here, we cloned GH, -GHR, somatolactin (SL), and somatolactin receptor (SLR) genes, and analyzed their expression patterns in different tissues and during early developmental stages by using real-time RT-PCR. We also further examined expression of them after acclimation to different salinity. Tissue distribution studies revealed that Km-GH and -SL mRNAs were remarkably expressed in brain and pituitary, whereas Km-GHR and -SLR mRNAs were predominantly expressed in liver, followed by gonad, muscle, pituitary, and brain. During embryonic developmental stages, the expression of their mRNA was increased at stage 3 (9 dpf). The Km-GH and -SL mRNA transcripts were constantly elevated until stage 5 (5h post hatch), whereas Km-GHR and -SLR mRNA levels decreased at this stage. After we transferred K. marmoratus from control (12 psu) to hyper-osmotic condition (hyperseawater, HSW; 33 psu), Km-GH, -SL, and GHR mRNA levels were enhanced. In hypo-osmotic conditions like freshwater (FW), Km-GH and -SL expressions were modulated 24 h after exposure, and Km-SLR transcripts were significantly upregulated. This finding suggests that Km-GH and -SL may be involved in the osmoregulatory mechanism under hyper-osmotic as well as hypo-osmotic stress. This is the first report on transcriptional modulation and relationship of GH, GHR, SL, and SLR during early development and after salinity stress. This study will be helpful to a better understanding on molecular mechanisms of adaptation response

  14. Hormonal treatment of acne vulgaris: an update

    Science.gov (United States)

    Elsaie, Mohamed L

    2016-01-01

    Acne vulgaris is a common skin condition associated with multiple factors. Although mostly presenting alone, it can likewise present with features of hyperandrogenism and hormonal discrepancies. Of note, hormonal therapies are indicated in severe, resistant-to-treatment cases and in those with monthly flare-ups and when standard therapeutic options are inappropriate. This article serves as an update to hormonal pathogenesis of acne, discusses the basics of endocrinal evaluation for patients with suspected hormonal acne, and provides an overview of the current hormonal treatment options in women. PMID:27621661

  15. Progestogens in menopausal hormone therapy

    Directory of Open Access Journals (Sweden)

    Małgorzata Bińkowska

    2015-06-01

    Full Text Available Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens.

  16. Modelling hormonal response and development.

    Science.gov (United States)

    Voß, Ute; Bishopp, Anthony; Farcot, Etienne; Bennett, Malcolm J

    2014-05-01

    As our knowledge of the complexity of hormone homeostasis, transport, perception, and response increases, and their outputs become less intuitive, modelling is set to become more important. Initial modelling efforts have focused on hormone transport and response pathways. However, we now need to move beyond the network scales and use multicellular and multiscale modelling approaches to predict emergent properties at different scales. Here we review some examples where such approaches have been successful, for example, auxin-cytokinin crosstalk regulating root vascular development or a study of lateral root emergence where an iterative cycle of modelling and experiments lead to the identification of an overlooked role for PIN3. Finally, we discuss some of the remaining biological and technical challenges. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. [Dehydroepiandrosterone (DHEA)--youth hormone?].

    Science.gov (United States)

    Zdrojewicz, Z; Kesik, S

    2001-01-01

    Dehydroepiandrosterone (DHEA) and its sulphated metabolite (DHEA-S) are endogenous steroid hormones, synthesized by the adrenal cortex, gonads and CNS. The secretion profile changes with age and depends on the sex. Human DHEA and DHEA-S levels decline linearly and systematically with age and suggest the potential importance of that parameter as a biomarker of ageing. The counteraction of DHEA against atherosclerotic disease, cancer growth, diabetes mellitus, insulin resistance, obesity and the influence on immunological functions are observed in researches. DHEA influences the condition of mind, cognition functions, memory and well-being. DHEA hormonal replacement therapy is expected to lengthen human life by the stoppage of physiological degeneration changes and prevention of age-related clinical disorders.

  18. Thyroid hormone disorders and sepsis.

    Science.gov (United States)

    Luo, Bin; Yu, Zhui; Li, Yinping

    2017-01-01

    Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called "low triiodothyronine (T3)" syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of thyroid hormone disorder in the development and prognosis of sepsis.

  19. Luteinizing hormone in testicular descent

    DEFF Research Database (Denmark)

    Toppari, Jorma; Kaleva, Marko M; Virtanen, Helena E

    2007-01-01

    . Insulin-like hormone-3 (INSL3) is suggested to be the main regulator of gubernacular development and therefore an apparent regulator of testicular descent. INSL3 production is also related to LH, and reduced INSL3 action is a possible cause for cryptorchidism. Cryptorchid boys have normal testosterone......A proper hypothalamus-pituitary-testis axis with normal androgen synthesis and action is a prerequisite for normal testicular descent. Various defects in this axis may result in cryptorchidism but endocrine abnormalities are rarely detected. Androgens regulate testicular descent but androgen action...... alone is not sufficient for normal testicular descent. The regulation of androgen production is influenced both by placental human chorionic gonadotropin (hCG) and pituitary luteinizing hormone (LH). There is evidence that the longer pregnancy continues, the more important role pituitary LH may have...

  20. Obesity and hormonal contraceptive efficacy.

    Science.gov (United States)

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  1. Growth hormone therapy in progeria.

    Science.gov (United States)

    Sadeghi-Nejad, Ab; Demmer, Laurie

    2007-05-01

    Catabolic processes seen in Hutchinson-Gilford progeria resemble those of normal aging and, in the affected children, usually result in death at an early age. In addition to its growth promoting effects, growth hormone (GH) has potent anabolic properties. Administration of GH ameliorates some of the catabolic effects of normal aging. We report the results of GH treatment in a young child with progeria.

  2. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  3. Thyroid Hormone Regulation of Metabolism

    Science.gov (United States)

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

  4. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  5. Growth hormone, inflammation and aging

    Directory of Open Access Journals (Sweden)

    Michal M. Masternak

    2012-04-01

    Full Text Available Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1 constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

  6. Thyroid hormone and seasonal rhythmicity

    Directory of Open Access Journals (Sweden)

    Hugues eDardente

    2014-02-01

    Full Text Available Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation and migration. At temperate latitudes, changes in photoperiod maintain the alignment of annual rhythms with predictable changes in the environment. The appropriate physiological response to changing photoperiod in mammals requires retinal detection of light and pineal secretion of melatonin, but extraretinal detection of light occurs in birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone conversion. Here we review the evidence that a circadian clock within the pars tuberalis of the adenohypophysis links photoperiod decoding to local changes of thyroid hormone signalling within the medio-basal hypothalamus through a conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond the photoperiodic control of its conversion, thyroid hormone might also be involved in longer term timing processes of seasonal programs. Finally, we examine the potential implication of kisspeptin and RFRP3, two RF-amide peptides expressed within the medio-basal hypothalamus, in seasonal rhythmicity.

  7. Thyroid hormone deiodination in birds.

    Science.gov (United States)

    Darras, Veerle M; Verhoelst, Carla H J; Reyns, Geert E; Kühn, Eduard R; Van der Geyten, Serge

    2006-01-01

    Because the avian thyroid gland secretes almost exclusively thyroxine (T4), the availability of receptor-active 3,3',5-triiodothyronine (T3) has to be regulated in the extrathyroidal tissues, essentially by deiodination. Like mammals and most other vertebrates, birds possess three types of iodothyronine deiodinases (D1, D2, and D3) that closely resemble their mammalian counterparts, as shown by biochemical characterization studies in several avian species and by cDNA cloning of the three enzymes in chicken. The tissue distribution of these deiodinases has been studied in detail in chicken at the level of activity and mRNA expression. More recently specific antibodies were used to study cellular localization at the protein level. The abundance and distribution of the different deiodinases shows substantial variation during embryonic development and postnatal life. Deiodination in birds is subject to regulation by hormones from several endocrine axes, including thyroid hormones, growth hormone and glucocorticoids. In addition, deiodination is also influenced by external parameters, such as nutrition, temperature, light and also a number of environmental pollutants. The balance between the outer and inner ring deiodination resulting from the impact of all these factors ultimately controls T3 availability.

  8. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    Science.gov (United States)

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-12-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  9. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-03-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  10. Hormone symphony during root growth and development.

    Science.gov (United States)

    Garay-Arroyo, Adriana; De La Paz Sánchez, María; García-Ponce, Berenice; Azpeitia, Eugenio; Alvarez-Buylla, Elena R

    2012-12-01

    Hormones regulate plant growth and development in response to external environmental stimuli via complex signal transduction pathways, which in turn form complex networks of interaction. Several classes of hormones have been reported, and their activity depends on their biosynthesis, transport, conjugation, accumulation in the vacuole, and degradation. However, the activity of a given hormone is also dependent on its interaction with other hormones. Indeed, there is a complex crosstalk between hormones that regulates their biosynthesis, transport, and/or signaling functionality, although some hormones have overlapping or opposite functions. The plant root is a particularly useful system in which to study the complex role of plant hormones in the plastic control of plant development. Physiological, cellular, and molecular genetic approaches have been used to study the role of plant hormones in root meristem homeostasis. In this review, we discuss recent findings on the synthesis, signaling, transport of hormones and role during root development and examine the role of hormone crosstalk in maintaining homeostasis in the apical root meristem.

  11. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh;

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  12. Expression of growth hormone and growth hormone receptor in fibroadenomas of the breast.

    Science.gov (United States)

    Lenicek, Tanja; Kasumović, Dino; Stajduhar, Emil; Dzombeta, Tihana; Jukić, Zoran; Kruslin, Bozo

    2013-06-01

    Fibroadenoma is the most prevalent benign breast tumor. It consists of epithelial and stromal components. In general, breast tumors are highly hormonally dependent and growth hormone by its physiology may have a possible oncogenic potential. Therefore, the aim of this study was to determine the expression of growth hormone and growth hormone receptor in epithelial and stromal components of fibroadenomas. Study group included 30 randomly chosen fibroadenomas from female patients aged between 18 and 69 years. The expression of growth hormone and growth hormone receptor was defined in both histologic components of fibroadenomas. Growth hormone was expressed in 96.7% of both epithelial and stromal components of fibroadenomas, with stronger expression in the stromal component. The same percentage of positive reaction (96.7%) was obtained in the epithelial component of fibroadenomas for growth hormone receptor expression. Only 6.7% of stromal components tested for growth hormone receptor were positive. The high expression of growth hormone and growth hormone receptor in fibroadenoma tissue indicates their possible role in the pathogenesis of this tumor. Follow up of patients with high expression of growth hormone and growth hormone receptor may be suggested.

  13. The thyroid hormone, parathyroid hormone and vitamin D associated hypertension

    Directory of Open Access Journals (Sweden)

    Sandeep Chopra

    2011-01-01

    Full Text Available Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two.

  14. Evaluating the function of putative hormone transporters.

    Science.gov (United States)

    Frommer, Wolf B; Schulz, Burkhard; Murphy, Angus S

    2009-02-01

    Hormones typically serve as long distance signaling molecules. To reach their site of action, hormones need to be transported from the sites of synthesis. Many plant hormones are mobile, thus requiring specific transport systems for the export from their source cells as well as subsequent import into target cells. Hormone transport in general is still poorly understood. Auxin is probably the most intensively studied plant hormone concerning transport in the moment. To advance our understanding of hormone transport we need two principal data sets: information on the properties of the transport systems including substrate specificity and kinetics, and we need to identify candidate genes for the respective transporters. Physiological transport data can provide an important basis for identifying and characterizing candidate transporters and to define their in vivo role. A recent publication in Plant Physiology highlights how kinetic and specificity studies may help to identify cytokinin transporters.

  15. Physical Activity and Obesity Related Hormones

    Directory of Open Access Journals (Sweden)

    Mehdi Hedayati

    2014-08-01

    Full Text Available Probably, obesity can be considered as the most common metabolic disorder. In other words, the control of metabolism is disrupted in this condition. The most important metabolic control is performed by hormones. Today, adipose tissue is considered as an active tissue in secretion of hormones. In obesity, in addition to adipose tissue hormones, effective neuropeptides on appetite are interfered. There are 4 main approaches in the management and treatment of obesity including nutrition and diet therapy, physical activity, medical and surgical approaches. The specialists and obese patients prefer the first and second approaches. Physical activity helps to control and treat this disorder by influencing on obesity-related hormones. The main obesity-related hormones are ghrelin, agouti, obestatin, leptin, adiponectin, nesfatin, visfatin, tumor necrosis factor, interleukin-6, and resistin. In this review, the effect of physical activity on 10 major obesity-related hormones has been discussed.

  16. Do hormones influence melanoma? Facts and controversies.

    Science.gov (United States)

    Gupta, Amie; Driscoll, Marcia S

    2010-01-01

    The issue of whether hormones influence malignant melanoma (MM) has been controversial for many years. Although early case reports demonstrated a negative effect of hormones, recent evidence has not supported a potential role for hormones in MM. We address whether exogenous and endogenous hormones influence a woman's risk for MM or affect her prognosis if diagnosed with MM. Multiple epidemiologic studies show the use of oral contraceptives or hormone replacement therapy does not appear to increase a woman's risk for MM. Pregnancy does not appear to influence a woman's risk of MM, nor does pregnancy appear to affect prognosis in the woman diagnosed with MM. When counseling the woman who is diagnosed with MM during pregnancy or during the childbearing years, future use of oral contraceptives or hormone replacement therapy is not contraindicated; counseling concerning future pregnancies should be done on a case-by-case basis, with emphasis placed on established prognostic factors for MM.

  17. Thyroid hormone metabolism in poultry

    Directory of Open Access Journals (Sweden)

    Darras V.M.

    2000-01-01

    Full Text Available Thyroid hormone (TH receptors preferentially bind 3.5,3'-triiodothyronine (T3. Therefore the metabolism of thyroxine (T4 secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T3, plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type 1 deiodinase (D1 catalyses both outer ring (ORD and inner ring deiodinalion (IRD. Type II deiodinase (D2 only catalyses ORD while type III (D3 only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels off, inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T3 availability and hence in

  18. Anticoncepción hormonal

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    1997-02-01

    Full Text Available Se realizó una revisión de los anticonceptivos hormonales con énfasis en aspectos que van desde su descubrimiento, el mecanismo de acción, los diferentes tipos y formas de utilización, así como el esquema de administración terapéutica en algunas entidades, sus indicaciones, ventajas y contraindicaciones: A review of the hormonal contraceptives was carried out, emphasizing on features from their discovery, trigger mechanism, different kinds, and ways to use them, as well as the scheme of the therapeutical administration in some entities, its indications, advantages, and contraindications.

  19. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...... in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment...

  20. Plant Hormones: Metabolism, Signaling and Crosstalk

    Institute of Scientific and Technical Information of China (English)

    Li-Jia Qu; Yunde Zhao

    2011-01-01

    @@ Plants synthesize various hormones in response to environmental cues and developmental signals to ensure their proper growth and development.Elucidation of the molecular mechanisms by which plant hormones control growth and development contributes to our understanding of fundamental plant biology and provides tools to improve crops.Because of their critical roles in plant growth and development, plant hormones have been studied extensively since the early days of plant biology.