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 investigate the mechanism underlying the GH-releasing effect of arginine (ARG), we studied the interactions of ARG (0.5 g/kg infused i.v. over 30 min) with GHRH (1 microgram/kg i.v.) and with pyridostigmine (PD, 60 mg orally) on GH secretion in 15 children and adolescents with familial short stature (5.1-15.4 years). In a group of eight subjects ARG induced a GH increase not statistically different to that observed after GHRH (peak, mean +/- SEM: 38.0 +/- 10.4 vs 64.0 +/- 14.4 mU/l). The combined administration of ARG and GHRH led to GH levels (101 +/- 15.2 mU/l) higher than those observed after GHRH (P less than 0.025) or ARG alone (P less than 0.001) and overlapping with those recorded after combined PD and GHRH administration (111 +/- 22.4 mU/l). In the other seven subjects, ARG and PD administration induced a similar GH response either when administered alone (25.2 +/- 13.6 and 27.8 +/- 4.0 mU/l, respectively) or in combination (33.8 +/- 5.4 mU/l). In conclusion, our results show that in children ARG administration potentiates GHRH- but not PD-induced GH increase. These findings agree with the hypothesis that the GH-releasing effect of both ARG and PD is mediated via the same mechanism, namely, by suppression of endogeneous somatostatin release. Combined administration of either ARG or PD with GHRH has a similar striking GH-releasing effect which is clearly higher than that of GHRH alone.
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PMID:Arginine potentiates the GHRH- but not the pyridostigmine-induced GH secretion in normal short children. Further evidence for a somatostatin suppressing effect of arginine. 197 84

To examine the effects of growth hormone-releasing factor (GRF) on islet hormone release, rat pancreas was perfused. rhGRF at the concentration of 10(-7) M or more enhanced insulin secretion stimulated by 16.7 mM glucose, hpGRF slightly enhanced insulin secretion as well. The insulin secretion induced by 10(-6) M rhGRF was completely inhibited by 10(-6) M propranolol. rhGRF at the concentration of 10(-8) M or more stimulated glucagon secretion even in the presence of 16.7 mM glucose. The glucagon secretion stimulated by 10(-6) M rhGRF was inhibited in the early period but increased thereafter by 10(-6) M propranolol. 10(-6) M rhGRF slightly stimulated glucagon secretion in the presence of 16.7 mM glucose when STZ diabetic rat pancreas was perfused. rhGRF at the concentration of 10(-6) M enhanced somatostatin secretion stimulated with 16.7 mM glucose. We concluded that rhGRF stimulated insulin, glucagon and somatostatin secretion and the insulin secretion was inhibited by beta-blocker. hpGRF stimulated insulin and glucagon secretion as well.
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PMID:[The effect of growth hormone-releasing factor (GRF) on secretion of insulin, glucagon and somatostatin from perfused rat pancreas]. 197 24

This work investigated in rats whether passive immunization against the endogenous GHRF in the early postnatal period led to permanent alterations of somatotropic function, similar to those observed in several human growth disorders, e.g. constitutional growth delay (CGD). On postnatal days 1, 2, 4, 6, 8, and 10, rats were given an anti-GHRF-serum (GHRH-Ab, 100 microliters/rat, sc) and were tested 1, 30, and 60 days after this treatment for basal and GHRH-stimulated GH secretion both in vivo and in vitro. GHRH-Ab reduced both basal and GHRF-stimulated GH secretion at all intervals and induced marked and chronic impairment of growth rate. The following differences were observed in the GHRH-Ab treated rats compared to normal rabbit serum-treated controls: 1) GH biosynthesis (incorporation of L-[3H]leucine into the electrophoretic band of GH): reduction of about 70%, 1 day but not 30 days after treatment; 2) Pituitary weight: significant reduction in absolute weight (30-40%) at all posttreatment intervals, and relative weight, 1 and 30 days after treatment. 3) Pituitary GH concentration: significant reduction in GH content (about 40%) but not concentration, at all posttreatment intervals; 4) Percentage of somatotrophs (immunocytochemistry): about 40% reduction 1 day, but not 30 and 60 days after treatment; 5) Hypothalamic somatostatin messenger RNA (mRNA) levels in situ hybridization): selective reduction (40%) in the periventricular nucleus 1 day but not 30 days after treatment; 6) Hypothalamic somatostatin cell number (immunocytochemistry): no significant changes in any hypothalamic area at any interval; 7) Pituitary somatostatin binding (in situ autoradiography): significant reduction, 1 day and 30 days after treatment; 8) Somatostatin inhibition of GH release "in vitro": somatostatin effect on GH release was reduced 30 days after treatment. These and previous data indicate that: 1) Transient deprivation of GHRF in the immediate postnatal period of the rat leads to permanent impairment of growth rate and somatotropic function; 2) GHRF deficiency itself or through reduction of GH secretion impairs somatostatin functions temporarily in the hypothalamus and permanently in the pituitary; 3) This rat model may mimic some forms of growth disorders in humans and holds promise as useful tools for investigating the underlying pathophysiological mechanisms.
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PMID:Deprivation of growth hormone-releasing hormone early in the rat's neonatal life permanently affects somatotropic function. 197 92

Somatostatin pretreatment sensitizes rat anterior pituitary to hGRF stimulation in vitro. The pretreatment (1 nM for 10 min) facilitated GH release response of dispersed rat anterior pituitary cells to hGRF (1 nM for 3 min) 2.04-fold in a perifusion system. The effect lasted even 20 min after the pretreatment. SRIF pretreatment decreased cAMP content in the cells after hGRF stimulation to 61% of the control value. When hGRF was replaced by 1 mM DBcAMP and 15 mM KCl, the pretreatment increased GH secretion 1.69- and 1.67-fold respectively. SRIF pretreatment (1 nM for 10 min) caused a larger increase in (Ca2+)i by hGRF than that of control. The effect of SRIF pretreatment facilitates GRF-induced increase in GH secretion probably through the stimulation of increase in (Ca2+)i.
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PMID:Somatostatin pretreatment facilitates GRF-induced GH release and increase in free calcium in pituitary cells. 197 87

The purpose of this study was to investigate the precise mechanism by which central alpha 2-adrenergic pathways modulate GH secretion in humans. In 10 normal subjects we compared the pattern of clonidine-induced GH release to that elicited by GH-releasing hormone (GHRH) given at a time of presumably similar responsiveness of the somatotrope. We also evaluated the effect of stimulation by GHRH (either endogenous, by administration of clonidine, or exogenous) on the GH response to a further exogenous GHRH stimulation. In 2 experiments the administration of clonidine (0.150 mg, orally) at 0 or 60 min was followed by a GHRH [GRF-(1-29); 1 micrograms/kg, iv] challenge at 180 min. In other experiments subjects received on separate occasions placebo or clonidine at 0 min, followed by GHRH at 60 min and again at 180 min. In a further experiment the administration of clonidine at 0 min was followed by 2 GHRH challenges (60 and 180 min later). The administration of clonidine 60 or 120 min, but not 180 min, before the GHRH bolus significantly (P less than 0.01) increased the GH responses to this challenge compared to those elicited by GHRH when given after placebo in a period of a similar somatotrope responsiveness. These, in turn, were significantly (P less than 0.05) higher than those elicited by clonidine alone. The close relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks, not observed for clonidine, was lost after pretreatment with this drug. These data indicate that clonidine was able to disrupt the intrinsic hypothalamic-somatotroph rhythm, suggesting that alpha 2-adrenergic pathways have a major inhibitory effect on somatostatin release. Our data also indicate that GH responses to a GHRH bolus administered 120 min after a prior GHRH challenge are dependent on two parameters: the intrinsic hypothalamic-somatotroph rhythm at the time of the second GHRH bolus, and the magnitude of GH secretion elicited by the previous somatotroph stimulation. In summary, alpha 2-adrenergic agonism appears to act primarily in GH control by inhibiting the hypothalamic release of somatostatin, rather than by stimulating GHRH secretion.
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PMID:Alpha 2-adrenergic agonism enhances the growth hormone (GH) response to GH-releasing hormone through an inhibition of hypothalamic somatostatin release in normal men. 197 61

It is now clear that both long-loop and ultrashort-loop feedback mechanisms may operate to autoregulate GH secretion at both central nervous system and pituitary levels. The key components of this control mechanisms involve GH itself, the GH-dependent peptides, somatomedins, and the two specific hypothalamic hypophysiotropic peptides GHRH and somatostatin. Presently, the intimate mechanism(s) and the respective contributions of the different components as well as the possible interactions between them under physiological or pathological conditions await clarification. However, a major role played by the hypothalamic release of somatostatin is clearly emerging. The awareness of GH autoregulation, and that the amounts of GH used for therapy are at or above the total daily GH production suggest caution in the institution of treatment with GH in children with idiopathic short stature, although resilience of the endogenous GH-secretory machinery would be present in these instances. Ideally, a GH replacement therapy should mimic the physiological secretory pattern of GH.
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PMID:Clinical implications of growth hormone feedback mechanisms. 197 30

The distribution of somatostatin and growth hormone releasing factor (GRF) fibres in the hypothalamus suggests that they may be involved in physiological functions in addition to growth hormone control. GRF or somatostatin were stereotaxically injected into anterior or basal hypothalamic regions of unanesthetized male rats and effects on plasma prolactin measured. Somatostatin caused a small, significant, dose-responsive stimulation of prolactin secretion when injected in both hypothalamic regions, while GRF was without effect. Somatostatin may therefore have a minor intrahypothalamic role in regulating prolactin.
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PMID:Intrahypothalamic injection of somatostatin, not GRF, stimulates prolactin secretion. 197 54

With the advent of genetic engineering, the importance of GH in the regulation of growth and metabolism in domestic species has been clearly demonstrated. Ample evidence of an integral role for GH in the processes of growth and lactation exists in dairy cattle (1,2), sheep (3), beef cattle (4) and swine (5). For example, circulating GH levels are high during the period of rapid growth in several species including cattle (6), swine (7) and poultry (8). Endogenous GH secretion is primarily controlled by the central nervous system (CNS) via two specific hypothalamic neurohormones, growth hormone-releasing factor (GRF) and somatostatin (SRIF), an inhibitor of GH release. The secretion of GRF and SRIF is governed by a host of neuropeptides and neurotransmitters which provide a functional link between higher CNS centers and hypophysiotropic neurons. This review will focus on the CNS regulation of GH secretion and circulating factors which feedback to either stimulate or inhibit its release.
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PMID:The neurophysiological regulation of growth hormone secretion. 197 64

Previous investigations of centrally administered somatostatin (SRIF) have tended to employ pharmacological (nmol and greater) doses of the peptide. Under this protocol contradictory findings of feeding effects have been reported. There is evidence that the use of physiological doses can induce a completely distinct response from that obtained with pharmacological doses. In order to discern whether physiological doses of centrally administered somatostatin have any effect on feeding. SRIF in doses ranging from 0.4 pmol to 3 nmol were administered into the lateral ventricles of rats. Low pmol doses (0.4-40) administered during the light photoperiod increased 1 h feeding whereas 3 nmol decreased 1 h feeding. None of the doses tested during the dark photoperiod significantly altered 1 h food intake. Similarly, no significant change in 24-h food intake was observed following injections of any of the doses tested, whether in the light or dark. A dose of SRIF that increased feeding (1 pmol) did not significantly alter 1 h water intake when applied centrally in the light nor did it alter spontaneous locomotor activity. Furthermore, when applied peripherally it did not change 1 h food intake. These studies suggest that SRIF may work centrally to regulate food intake. A similarity exists between SRIF's feeding effects and the feeding effects we have previously described following central injections of growth hormone-releasing factor (GRF), both in terms of dose-response and photosensitivity. This suggests that these 2 peptides may act via a common mechanism to regulate food consumption; possibly in co-ordination with their regulation of growth hormone release. The possibility that such feeding regulation occurs as part of a short intrahypothalamic feedback loop is discussed.
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PMID:Central somatostatin: a re-examination of its effects on feeding. 198 89

To establish a single and reliable test for evaluating GH secretion, we examined successive GH provocation by two agents with different modes of action: GHRH and arginine (Arg). In 4 normal subjects, a bolus injection of 50 micrograms of GHRH followed by 0.5 g/kg Arg infusion after 90 min evoked two GH peaks and the priming of the GHRH potentiated Arg-induced GH peak by 88% of that by Arg alone. In contrast, Arg pretreatment suppressed the GHRH-induced GH peak to a level of 15%. This inhibitory effect of Arg priming was not recovered by an increase in the GHRH dose (100 micrograms) or by prolongation of the GHRH injection period to 180 min. During Arg infusion, plasma somatostatin (SRIH) was significantly reduced and there was a linear correlation between Arg-induced GH peaks and basal TSH levels. This suggests that GH release by Arg is mediated by suppression of hypothalamic SRIH. One subject showed a blunted GH peak in response to GHRH but a normal peak in response to Arg repeatedly, suggesting an endogenous hypertonicity of SRIH. In 4 other normal subjects, the effect of endogenous GH fluctuation on the GHRH-Arg test was examined in the morning, afternoon and evening. The GH secretory profile was fairly consistent in individuals, but in 2 of them, GH response to GHRH was exaggerated in the evening and Arg-unresponsiveness ensued. This potentiation of GH release appears to be due to an increase in endogenous GHRH secretion or a decrease in SRIH tone. The GHRH-Arg test is therefore able to evaluate GH secretory dynamics through two major mechanisms, GHRH stimulation and SRIH inhibition in a single procedure, reducing the incidence of false negative GH response to Arg.
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PMID:Mutual priming effects of GHRH and arginine on GH secretion: informative procedure for evaluating GH secretory dynamics. 198 90


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