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)

To clarify the direct effects of ghrelin on growth hormone (GH) release from anterior pituitary (AP) cells in cattle, GH-releasing effects of human ghrelin (hGhrelin) and rat ghrelin (rGhrelin) on bovine AP cells were compared with those of GH-releasing hormone (GHRH) in vitro. The AP cells were obtained from Holstein steers and were incubated for 2 h with the peptides after incubating in DMEM for 3 days. hGhrelin and rGhrelin significantly stimulated GH release from the cultured cells at doses from 10(-10) to 10(-7) M and from 10(-9) to 10(-7) M, respectively (P<0.05). The rates of increase in GH at 10(-10), 10(-9), 10(-8) and 10(-7) M hGhrelin were 26, 26, 59 and 100% compared with controls, respectively, and those of increase in GH at 10(-9), 10(-8) and 10(-7) M rGhrelin were 58, 74 and 106%, respectively. GHRH significantly increased GH concentrations in cultured media at a dose as low as 10(-13) M compared with the control (P<0.05). When hGhrelin (10(-8) M) and GHRH (10(-8) M) were added together, the release of GH induced by both peptides was significantly greater than that by hGhrelin alone (P<0.05), and tended to be greater than that by GHRH alone. Somatostatin (SS, 10(-7) M) significantly blunted GH release induced by hGhrelin (10(-8) M) and GHRH (10(-8) M) (P<0.05). In the presence of SS, the percent increase in GH released with hGhrelin plus GHRH was 42% and 14% greater than that by either hGhrelin or GHRH alone, respectively (P<0.05). These results show that ghrelin directly stimulates the release of GH from anterior pituitary cells, and that SS modifies ghrelin-stimulated GH release in cattle.
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PMID:Effects of ghrelin on growth hormone secretion from cultured adenohypophysial cells in cattle. 1294 Apr 57

Current investigational tools in molecular biology, biochemistry and integrative physiology have revealed an increasing array of signals that influence growth hormone (GH) secretion. The present perspective combines these factors under a simplified final-common pathway model of threefold joint control by GH-releasing hormone, GH-releasing peptide/ghrelin and somatostatin. This concept is highlighted from the viewpoint of sex steroid- and age-dependent modulation of the peptide trilogy listed above.
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PMID:A tripeptidyl ensemble perspective of interactive control of growth hormone secretion. 1295 24

Ghrelin is a newly discovered peptide that binds the receptor for GH secretagogues (GHS-R). The presence of both ghrelin and GHS-Rs in the hypothalamic-pituitary system, together with the ability of ghrelin to increase GH release, suggests a hypophysiotropic role for this peptide. To ascertain the intracellular mechanisms mediating the action of ghrelin in somatotropes, we evaluated ghrelin-induced GH release from pig pituitary cells both under basal conditions and after specific blockade of key steps of cAMP-, inositol phosphate-, and Ca2+-dependent signaling routes. Ghrelin stimulated GH release at concentrations ranging from 10-10 to 10-6 m. Its effects were comparable with those exerted by GHRH or the GHS L-163,255. Combined treatment with ghrelin and GHRH or L-163,255 did not cause further increases in GH release, whereas somatostatin abolished the effect of ghrelin. Blockade of phospholipase C or protein kinase C inhibited ghrelin-induced GH secretion, suggesting a requisite role for this route in ghrelin action. Unexpectedly, inhibition of either adenylate cyclase or protein kinase A also suppressed ghrelin-induced GH release. In addition, ghrelin stimulated cAMP production and also had an additive effect with GHRH on cAMP accumulation. Ghrelin also increased free intracellular Ca2+ levels in somatotropes. Moreover, ghrelin-induced GH release was entirely dependent on extracellular Ca2+ influx through L-type voltage-sensitive channels. These results indicate that ghrelin exerts a direct stimulatory action on porcine GH release that is not additive with that of GHRH and requires the contribution of a multiple, complex set of interdependent intracellular signaling pathways.
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PMID:Intracellular signaling mechanisms mediating ghrelin-stimulated growth hormone release in somatotropes. 1296 33

The peptide hormone ghrelin binds to the GH secretagogue receptor (GHS-R), stimulates GH secretion, and promotes adipogenesis. However, continuous GHS infusion does not stimulate skeletal growth and is associated with desensitization to further GH secretagogue treatment. In this study, 7-d intermittent (i.e. every 3 h) infusion of ghrelin, or the GH secretagogue, GH-releasing peptide-6, in the moderately GH- deficient transgenic growth-retarded rat, augmented GH secretion, leading to a sustained acceleration in skeletal growth. In contrast, continuous infusion of ghrelin, or GH-releasing peptide-6, suppressed the amplitude of spontaneous GH secretory episodes and produced only a transient increase in body weight gain. The reduction in GH secretion seen with continuous GHS-R activation was not associated with a desensitization of the pituitary to GH-releasing factor or to down-regulation of hypothalamic GHS-R mRNA expression. Continuous ghrelin treatment elicited an increase in somatostatin mRNA expression in the periventricular nuclei. Thus, exposure to continuously elevated circulating ghrelin may be responsible for the suppression of GH secretion reported in rats after prolonged starvation.
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PMID:Pattern-dependent suppression of growth hormone (GH) pulsatility by ghrelin and GH-releasing peptide-6 in moderately GH-deficient rats. 1296 77

Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 +/- 0.6, 4.7 +/- 0.8, and 4.5 +/- 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 +/- 0.27 vs. 4.67 +/- 1.24 ng.ml(-1).min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 +/- 0.27 vs. 3.18 +/- 0.92 ng.ml(-1).min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 +/- 46 vs. 514 +/- 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 +/- 46 vs. 546 +/- 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.
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PMID:Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy. 1455 25

The stimulation of exocrine pancreatic secretion that has been attributed by Pavlov exclusively to various reflexes (nervism), was then found that it depend also on numerous enterohormones, especially cholecystokinin (CCK) and secretin, released by duodeno-jejunal mucosa and originally believed to act via an endocrine pathway. Recently, CCK and other enterohormones were found to stimulate the pancreas by excitation of sensory nerves and triggering vago-vagal and entero-pancreatic reflexes. Numerous neurotransmitters and neuropeptides released by enteric nervous system (ENS) of gut and pancreas have been also implicated in the regulation of exocrine pancreas. This article was designed to review the contribution of vagal nerves and entero-hormones, especially CCK and other enterohormones, involved in the control of appetitive behavior such as leptin and ghrelin and pancreatic polypeptide family (peptide YY and neuropeptide Y). Basal secretion shows periodic fluctuations with peals controlled by ENS and by motilin and Ach. Plasma ghrelin, that is considered as hunger hormone, increases under basal conditions, while plasma leptin falls to the lowest level. Postprandial pancreatic secretion, classically divided into cephalic, gastric and intestinal phases, involves predominantly CCK, which under physiological conditions acts almost entirely by activation of vago-vagal reflexes to stimulate the exocrine pancreas, being accompanied by the fall in plasma ghrelin and increase of plasma leptin, reflecting feeding behavior. We conclude that the major role in postprandial pancreatic secretion is played by vagus and gastrin in cephalic and gastric phases and by vagus in conjunction with CCK and secretin in intestinal phase. PP, PYY somatostatin, leptin and ghrelin that affect food intake appear to participate in the feedback control of postprandial pancreatic secretion via hypothalamic centers.
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PMID:Brain-gut axis in pancreatic secretion and appetite control. 1456 70

Ghrelin stimulates appetite and plays a role in the neuroendocrine response to energy balance variations. Ghrelin levels are inversely associated with body mass index (BMI), increased by fasting and decreased by food intake, glucose load, insulin, and somatostatin. Ghrelin levels are reduced in obesity, a condition of hyperinsulinism, reduced GH secretion, and hypothalamus-pituitary-adrenal axis hyperactivity. We studied the endocrine and metabolic response to acute ghrelin administration (1.0 microg/kg i.v.) in nine obese women [OB; BMI (mean +/- SD) 36.3 +/- 2.3 kg/m(2)] and seven normal women (NW; BMI 20.3 +/- 1.7 kg/m(2)). Basal ghrelin levels in NW were higher than in OB (P < 0.05). In NW, ghrelin increased (P < 0.05) GH, prolactin (PRL), ACTH, cortisol, and glucose levels but did not modify insulin. In OB, ghrelin increased (P < 0.01) GH, PRL, ACTH, and cortisol levels. The GH response to ghrelin in OB was 55% lower (P < 0.02) than in NW, whereas the PRL, ACTH, and cortisol responses were similar. In OB, ghrelin increased glucose and reduced insulin (P < 0.05). Thus, obesity shows remarkable reduction of the somatotroph responsiveness to ghrelin, suggesting that ghrelin hyposecretion unlikely explains the impairment of somatotroph function in obesity. On the other hand, in obesity ghrelin shows preserved influence on PRL, ACTH, and insulin secretion as well as in glucose levels.
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PMID:Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity. 1460 93

To test the clinical hypothesis that an estrogen-enriched milieu enhances GHRH action, we administered placebo (Pl) and estradiol-17 beta (E(2)) orally for 23 d to six postmenopausal women in a prospectively randomized, double-masked, within-subject crossover design with 6 wk intervening. The GHRH stimulation protocol entailed consecutive i.v. infusion of L-arginine and a single i.v. pulse of saline or one of five randomly ordered doses of recombinant human GHRH-1,44-amide (0.03, 0.1, 0.3, 1.0, or 3.0 microg/kg) in a total of 12 separate morning, fasting sessions. GH secretion was monitored by sampling blood every 10 min for 6 h; chemiluminescence assay of GH concentrations; deconvolution analysis of stimulated GH release; and nonlinear dose-response reconstruction. Supplementation with E(2), compared with Pl: 1) increased (mean +/- SEM) E(2) concentrations from 18 +/- 3 (Pl) to 164 +/- 12 pg/ml (to convert to picomoles per liter, multiply by 3.57) (P < 0.001); 2) decreased IGF-I concentrations from 181 +/- 14 to 120 +/- 11 microg/liter (P < 0.01); 3) elevated mean GH concentrations from 0.27 +/- 0.06 to 0.59 +/- 0.08 microg/liter (P = 0.014); 4) potentiated GH secretion stimulated by L-arginine alone by 1.43-fold (P = 0.012); 5) reduced the ED(50) of GHRH from 0.27 +/- 0.02 to 0.13 +/- 0.01 microg/kg (P < 0.01), denoting enhanced GHRH potency; and 6) heightened the maximal slope of the dose-response function from 1.1 +/- 0.1 to 1.4 +/- 0.05 [( microg/liter) ( microg/kg)(-1)] (P < 0.05), signifying augmented pituitary sensitivity. The foregoing facilitative mechanisms were specific because E(2) replacement did alter maximal L-arginine/GHRH-induced GH secretion, indicating unchanged secretagogue efficacy. In conclusion, inasmuch as E(2) also attenuates inhibition of GH secretion by infused somatostatin and potentiates stimulation of GH secretion by GH-releasing peptide-2, we postulate that estrogenic steroids drive pulsatile GH production in part via mechanisms that include all three of GHRH, somatostatin, and putatively GH-releasing peptide/ghrelin signaling.
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PMID:Estradiol supplementation enhances submaximal feed-forward drive of growth hormone (GH) secretion by recombinant human GH-releasing hormone-1,44-amide in a putatively somatostatin-withdrawn milieu. 1460 94

The pulsatile release of growth hormone (GH) from anterior pituitary gland is regulated by the interplay of at least two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. Furthermore, release of GH in vivo may also be controlled by a third type of receptor, the growth hormone secretagogue receptor, a G-protein-coupled receptor, called GHS receptor type 1a (GHSR1a), which was identified in the pituitary and the hypothalamus in humans using a nonpeptidyl growth hormone secretagogue (MK-0677). Ghrelin, the endogenous ligand for the GHS-R1a, is a 28-amino-acid peptide isolated from human stomach that is modified by a straight chain octanoyl group covalently linked to Ser3, which is essential for its endocrine activity. This hormone, predominantly expressed and secreted by the stomach, has a dual action on GH secretion and food intake, showing interdependency between these actions. The finding that fasting and food intake, respectively, increase and decrease the secretion of ghrelin suggests that this hormone may be the bridge connecting somatic growth and body composition with energy metabolism, and appears to play a role in the alteration of energy homeostasis and body weight in pathophysiological states such as hypothyroidism and hyperthyroidism. Despite this, little is known about the intracellular signaling through which ghrelin exerts its regulatory actions. Activation of intracellular calcium mobilization is one of the earliest known cellular signals elicited by ghrelin. In HEK- 293 cells expressing the GHS-R1a, ghrelin induces a biphasic cytosolic calcium elevation characterized by a spike phase of the response, which reflects Ins(1,4,5)P3- dependent calcium mobilization of intracellular stores, and a sustained phase of the response, which is due to calcium influx across the plasma membrane triggered by aperture of capacitative calcium channels (store-operated calcium channels). Upon repeated administration, ghrelin showed a marked suppression of ghrelin-mediated elevations of intracellular calcium. This homologous desensitization represents an important physiological mechanism that modulates receptor responsiveness and acts as an information filter for intracellular signaling system. The discovery of ghrelin adds a new component to the complex machinery responsible for regulation of GH secretion in connection with the regulation of appetite and energy homeostasis.
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PMID:Regulation of ghrelin secretion and action. 1461 Feb 93

Technical, genetic, and clinical developments have unveiled a burgeoning array of novel effectors of GH secretion. The present appraisal of central neuroregulatory components of the somatotropic axis highlights a simplifying concept of ensemble control by the final common peptides, GH-releasing hormone (GHRH), GH-releasing peptide(s) (GHRP, ghrelin), and somatostatin. These potent signals act individually, antagonistically, and synergistically to direct pulsatile GH secretion. GHRH, GHRP/ghrelin, and somatostatin further adapt to autonegative feedback by GH and IGF-I. Estradiol modulates the impact of each of the primary peptidyl inputs; viz.: (i) enhances submaximally effective feedforward by discrete pulses of (injected) recombinant human GHRH-1,44-amide (as defined by increased agonistic potency and pituitary sensitivity); (ii) potentiates the submaximally stimulatory effects of GHRP-2, a hexapeptidyl mimetic of ghrelin; (iii) blunts dose-dependent inhibition of fasting GH secretion by somatostatin- 14; and (iv) relieves rhGH-enforced negative feedback on GHRP-2 (but not on basal, exercise, or GHRH)-stimulated GH secretion. The foregoing estrogenic activities collectively augment GH secretory burst mass by amplifying feedforward (via both GHRH and GHRP) and attenuating feedback (imposed by somatostatin and GH). Whether testosterone fully mimics the foregoing mechanistic actions of estradiol is not known. In conclusion, the present conceptual platform of tri-peptide-directed feedforward and GH/IGF-I-mediated feedback should aid in unraveling some of the complex regulatory dynamics targeted by sex-steroid hormones.
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PMID:Sex-steroid modulation of growth hormone (GH) secretory control: three-peptide ensemble regulation under dual feedback restraint by GH and IGF-I. 1461 Feb 96


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