Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary GH secretion is regulated by Ca+2 and cAMP. We show that human pancreatic tumor GRF (hpGRF) stimulates anterior pituitary adenylate cyclase activity, cAMP accumulation, and GH release. The relationship between Ca+2 and the stimulating effects of the Ca+2 ionophore A23187 on cAMP accumulation and GH release in vitro was studied. To evaluate the role of the Ca+2-binding protein calmodulin in this system, we used the calmodulin antagonist W7, a naphthalene-sulfonamide derivative, and its less active analog W5. W7 inhibited hpGRF-stimulated adenylate cyclase activity, cAMP accumulation, and GH release, whereas W5 was either poorly effective or ineffective. Somatostatin (SRIF) also attenuated hpGRF stimulation of adenylate cyclase. These results suggest that the actions of Ca+2-calmodulin and cAMP are interrelated in modulating GH release. Calmodulin participates in hpGRF stimulation of adenylate cyclase, cAMP formation, and GH release. The attenuation of hpGRF-stimulated adenylate cyclase activity by SRIF may be one of the mechanisms for its GH inhibitory action.
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PMID:Human pancreatic tumor growth hormone-releasing factor stimulates anterior pituitary adenylate cyclase activity, adenosine 3',5'-monophosphate accumulation, and growth hormone release in a calmodulin-dependent manner. 614 31

Pituitary glands from a teleost fish were incubated in the presence of the synthetic hypophysiotropic peptides, thyrotrophin-releasing hormone and somatostatin, in two media of different osmotic pressure. The effects on prolactin and growth hormone cells were detected by electron-microscopic morphometry with the aid of an image analyser. Thyrotrophin-releasing hormone caused changes in prolactin cell ultrastructure consistent with stimulated hormone release and, in the low osmotic pressure medium, appeared to increase synthetic activity. There was no effect on growth hormone cells. After somatostatin treatment, both synthesis and release in prolactin cells appeared to be inhibited, and there was an obvious inhibition of synthesis and release in growth hormone cells. The response of both cell types to somatostatin did not appear to be dependent on the osmotic pressure of the medium.
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PMID:Effects of TRH and somatostatin on releases of prolactin and growth hormone in vitro by the pituitary of Poecilia latipinna. II. Electron-microscopic morphometry using automatic image analysis. 614 21

With the availability of synthetic analogues of the hypothalamic releasing hormones, analysis of their interactions with pituitary receptors has been achieved. The most studied is gonadotrophin-releasing hormone (GnRH). Pituitary receptors for this peptide show a positive correlation with gonadotrophin secretion and responsiveness to exogenous GnRH in experimental animals, an indication of their physiological importance. GnRH is also required for maintenance of a 'normal' complement of GnRH receptors and, when administered intermittently, can effect significant increases in unoccupied receptors. Conversely, the continuous administration of high GnRH or agonist analogue (GnRH-A) doses leads to pituitary desensitization through disruption of receptor-mediated events. Thus, for stimulation of fertility using GnRH, the peptide should be administered in small doses at physiological frequency (approximately once every two hours) to avoid pituitary desensitization. The desensitizing properties of long-acting GnRH-A are of potential value as contraceptives agents and where a medical castration is desirable. The physiological correlates of pituitary receptors for thyrotrophin-releasing hormone, somatostatin (GHRIH) and corticotrophin-releasing factor await elucidation.
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PMID:Hypothalamic releasing-hormone receptors. 630 45

Most neuropeptides can now be assayed in human cerebrospinal fluid (CSF). Some, such as beta-endorphin and arginine vasopressin, seem to be secreted directly into CSF. Others may reach CSF from plasma either by passage through the blood-brain barrier or by absorption through the circumventricular organs, which lack a blood-brain barrier. The role of neuropeptides in CSF is still unclear. Thyrotropin-releasing hormone, somatostatin, arginine vasopressin, angiotensin II, substance P, vasoactive intestinal polypeptide, beta-endorphin, gastrin, and cholecystokinin are all present in assayable quantities in human CSF. Their functions in this fluid are liable to be as diverse as their functions elsewhere in the body. The release of hypothalamic releasing factors into the CSF may be part of the pathway of pituitary hormone release. Pituitary hormones may function in CSF as part of a feedback loop from the hypothalamus. Other neuropeptides may affect receptors in the central nervous system far away from their release site. Intraventricular neuropeptide injection, anatomical and physiological ablation experiments, receptor studies, and neurobiological techniques now being developed will allow a more complete understanding of CSF neuropeptide function in the future.
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PMID:Neuropeptides in cerebrospinal fluid. 675 95

We examined the chronic (72 h) effects of 30 ng/ml recombinant murine tumor necrosis factor (TNF)-alpha on release of immunoreactive growth hormone (GH), prolactin (PRL), thyrotropin (TSH), and TSH glycosylation, as assessed by lectin binding, in cultured rat anterior pituitary cells. In cultured cells from adult female rats, TNF-alpha significantly suppressed basal and GH-releasing hormone (GRH)-stimulated GH release. TNF-alpha also suppressed basal PRL release and completely abolished the PRL response to TRH (0.1-10 nM). Whereas TNF-alpha reduced basal TSH release, it significantly enhanced the maximal TSH response to TRH. TNF-alpha did not affect the concanavalin A and lentil lectin binding of TSH accumulated in the medium during the 4-day culture, but significantly decreased the lentil lectin binding of TSH released in response to acute TRH stimulation. TNF-alpha significantly enhanced the inhibitory effect of somatostatin on stimulated PRL release, but not on GH or TSH release. Compared to cell cultures from adult female rats, in anterior pituitary cell cultures from 12-day-old rats the effects of prolonged exposure to TNF-alpha on hormone release were diminished or absent. Pituitary hormone release was unaffected by acute (3 h) exposure to TNF-alpha. These results demonstrate a direct effect of TNF-alpha on anterior pituitary hormone release, which is cell-type specific and age dependent.
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PMID:Prolonged effects of tumor necrosis factor-alpha on anterior pituitary hormone release. 747 97

The five somatostatin receptor mRNAs are expressed with distinct though overlapping patterns of distribution in the CNS and peripheral tissues. All receptor types are expressed in the anterior pituitary and hypothalamus and could therefore be modulated in states of growth hormone (GH) dysregulation. Metabolic perturbations such as food deprivation and diabetes mellitus lead to suppression of GH levels in the rat, in part due to increased somatostatin tone. In rats deprived of food, pituitary sstr1, 2 and 3 mRNAs were reduced by 80% compared to fed controls; sstr4 and sstr5 mRNAs were unchanged. Hypothalamic sstr mRNA expression was unaltered. In diabetic rats pituitary sstr1, 2 and 3 mRNAs were reduced by 50-80% with sstr1 mRNA restored in part by insulin therapy. Pituitary sstr4 mRNA and hypothalamic expression of these four types was unaffected. sstr5 mRNA is reduced by 70% in the pituitary and by 30% in the hypothalamus with restoration of both by insulin treatment. Altered pituitary sstr expression in food deprivation and diabetes could result from chronic exposure to increased plasma somatostatin. In rat GH3 pituitary tumour cells exposed to 1 microM somatostatin for up to 48 h, sstr1, 3, 4 and 5 mRNA increased dramatically while sstr2 mRNA exhibited a biphasic response. We observed a net increase in receptor binding associated with increased sstr mRNA. Somatostatin receptor expression is regulated in a tissue- and type-specific manner, adding further complexity to the action of the multifaceted peptide somatostatin.
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PMID:Regulation of somatostatin receptor mRNA expression. 758 42

GH secretory patterns undergo marked change during early mammalian development. The factors that underlie these changes and the major components of signal transduction in the immature somatotrophs are not fully understood. Increasing evidence suggests that protein kinase C (PKC) plays a central role in perinatal organ differentiation and function. To evaluate the possible role of PKC as a mediator of GH secretion from immature pituitaries, we tested the effects of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or together with GH-releasing factor (GRF), somatostatin (SRIF), and Ca2+ modifying agents; an inactive phorbol analogue (4 alpha-12-13-didecanoate; 4 alpha-PDD), and phospholipase C on GH release from pituitary cell cultures from perinatal and mature rats. Pituitary primary cell cultures were prepared from fetal (day 20 of 21.5 days of gestation), 2-day-old, 12-day-old, and adult male (2- to 4-month-old) rats. Each experiment was performed on at least three separate occasions. The magnitude of TPA (0.15-150 nM)-induced GH release was markedly age-dependent, fractional GH release being greatest from pituitaries of fetal and newborn rats, and least from those of adults (P < 0.001). Further, the minimum dose of TPA required to stimulate GH release over basal levels was tenfold higher for adult pituitaries (15 nM) than for perinatal pituitaries (1.5 nM). Phospholipase C (1 and 10 U/ml) also caused greater fractional GH release from neonatal pituitaries than from adult pituitaries (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of the GH response to phorbol ester and phospholipase C in rat pituitary cells. 761 64

The hypothalamo-pituitary-gonadotrophic axis develops in the sheep fetus from midgestation to late gestation. The GnRH neuronal centres seem to be fully developed in the fetus and their localization complies with the adult pattern. Pituitary gonadotrophs are responsive to exogenous GnRH and release LH and FSH in a pulsatile fashion; the highest concentrations in plasma are found during late gestation. In sheep, maturational changes of this axis continue through to the prepubertal period. The GnRH neuronal system is established at about 12 weeks of age. The pattern of LH and FSH release is characteristic for each gonadotrophin depending on age and sex. The responsiveness of the gonadotrophs to GnRH increases up to 3 weeks of age. It is concluded that the changes in morphology and physiology of the hypothalamo-pituitary-gonadotrophic axis reflect the progressive maturation of the central mechanisms involved in the control of gonadotrophin secretion throughout fetal and prepubertal growth in sheep. Development of the hypothalamo-pituitary-somatotrophic axis begins in the fetus around mid-gestation. The central regulation of growth hormone (GH) in the fetus probably has a dual character, although the growth hormone releasing hormone (GHRH) neuronal system has not yet been observed in sheep. The somatostatin neuronal system develops in diverse neuronal centres in the fetus. The somatostatin centre involved in hypophysiotrophic functions does not develop fully before birth and is established over the first 10 weeks after birth. Plasma GH concentrations are very high in the fetus and fall suddenly in the perinatal period, and after a temporary increase they decline with age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of the gonadotrophic and somatotrophic axes of sheep. 762 13

Pituitary-specific expression of the GH gene is dependent on a pituitary-specific transcription factor GH factor-1 (GHF-1), a homeodomain protein also known as pituitary-specific transcription factor-1 (Pit-1). The aim of this study was to investigate the regulation of GHF-1 messenger RNA (mRNA) levels in primary monolayer cultures of rat anterior pituitary cells. Specifically, in addition to direct activators of second messenger signaling systems, we studied the effects of different hormones, all of which are known to be involved in the regulation of somatotroph cell function. We found that GH-releasing hormone (GHRH) increased GHF-1 mRNA levels in a time- and dose-dependent fashion. GHF-1 mRNA levels were increased 2.5-fold (P < 0.01) after incubation for 2 h with 10(-8) M GHRH. Longer incubations (6, 12, or 24 h) with GHRH failed to show a similar stimulatory effect. A significant increase in GHF-1 mRNA concentration (1.7-fold, P < 0.01) was observed after a 2-h treatment with physiological concentrations (10(-11) M) of GHRH. The action of GHRH seems to occur at the transcriptional level without the need of protein synthesis. Thus, treatment of cells with actinomycin D (5 micrograms/ml) completely abolished GHRH-induced increase in GHF-1 mRNA levels. Cycloheximide (23 micrograms/ml) alone increased GHF-1 mRNA levels (6-fold increase after treatment for 12 h, P < 0.01), as well as potentiating GHRH-induced increase in GHF-1 mRNA concentration (9-fold increase after treatment with GHRH plus cycloheximide for 12 h, P < 0.01). The effect of GHRH on GHF-1 mRNA levels could be mimicked by direct activators of second messenger signaling systems such as forskolin (10(-5) M) or the phorbol ester tumor promoter tetradecanoyl phorbol acetate (TPA) (10(-6) M). Other peptides such as pituitary adenylate cyclase activating polypeptide-38 (10(-7) M) but not GHRP-6 (10(-10) to 10(-5) M), were also able to increase GHF-1 mRNA levels. Treatment of the cells with somatostatin (10(-6) M) for either 2 or 48 h failed to modify basal or GHRH-induced GHF-1 mRNA levels. In contrast, pretreatment of the cells with insulin-like growth factor-1 (5 nM) inhibited basal GHF-1 mRNA concentration as well as completely blunting the subsequent response to cells exposed to GHRH for 2 h. These data demonstrate that GHRH, acting at the transcriptional level and through a mechanism not dependent on protein synthesis, plays a stimulatory role on GHF-1 mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of the pituitary-specific transcription factor GHF-1/Pit-1 messenger ribonucleic acid levels by growth hormone-secretagogues in rat anterior pituitary cells in monolayer culture. 764 93

Transgenic mice expressing a tyrosine hydroxylase-human (h) GH fusion gene in the hypothalamus exhibit a dwarf phenotype. The GH feedback mechanism(s) underlying the growth retardation in these animals was investigated by assessing peptide and messenger RNA (mRNA) levels of the hormones of the hypothalamic-GH-IGF-I axis. Pituitary GH content, hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) content, and serum IGF-I levels were measured by RIA. mRNA levels of hypothalamic GHRH and SRIH and of pituitary GH and the GHRH receptor were measured by Northern blot hybridization. Transgenic mice of both sexes and their wild-type littermates were studied at 2-4 months of age. The pituitary GH content was markedly reduced by 85% in male and by 87% in female transgenic mice compared to that in wild-type controls (P < 0.01 for both). The pituitary GH mRNA content was also decreased by 73% (P = 0.002) in transgenic male mice. Circulating IGF-I levels were significantly reduced by 66% and 68% in male and female transgenic mice, respectively (P = 0.001). The hypothalamic GHRH content was significantly reduced by 19% and 33% (P < 0.05) in male and female transgenic mice, respectively. No significant difference was detected, however, in the hypothalamic SRIH content between wild-type and transgenic mice. Hypothalamic GHRH mRNA levels were significantly decreased by 35% (P = 0.002) in transgenic male mice compared to those in wild-type littermates. In contrast, SRIH mRNA was not significantly changed. An even greater reduction (61%; P = 0.003) was observed in pituitary GHRH receptor mRNA in transgenic mice. These data indicate that the GH deficiency and dwarf phenotype of the tyrosine hydroxylase-hGH transgenic mouse can be attributed primarily to impaired hypothalamic GHRH production. The mechanism of GH feedback inhibition appears to involve direct suppression of GHRH gene expression by locally produced hGH in the hypothalamus.
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PMID:Autofeedback suppression of growth hormone (GH) secretion in transgenic mice expressing a human GH reporter targeted by tyrosine hydroxylase 5'-flanking sequences to the hypothalamus. 764 13


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