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)

The effects of rat growth hormone releasing factor (rGRF) on somatostatin (SRIF) secretion, cyclic nucleotide production and phosphatidylinositol metabolism were investigated in the median eminence (ME), using an in vitro system. Medium was discarded and replaced by medium containing various concentrations of rGRF or rGRF plus epinephrine (E, 6 x 10(-7) M). rGRF had no effect on basal or E-stimulated release of cAMP. In the same experiments rGRF markedly stimulated SRIF release. These results suggested that cAMP is not involved in the stimulatory effect of GRF on SRIF release. However, GRF significantly stimulated release of both SRIF and cGMP in a dose-related manner. Maximal stimulation was observed at 10(-10) M GRF (p less than 0.005) which also produces maximal SRIF release. 2'0-monobutyrylguanosine 3'5' cyclic phosphate (mbcGMP, 10(-11) to 10(-10) M) stimulated SRIF release from ME fragments (p less than 0.001 at 10(-10) M) whereas the control, sodium butyrate (10(-6) M), had no effect. GRF caused significant elevation of 30.6% in the concentration of labelled inositol phosphates [( 3H]-IPs) in the ME. These data indicate that GRF stimulation of SRIF release is accompanied by increased cGMP production and phosphatidyl-inositol (PI) metabolism but does not alter cAMP production. Because mbcGMP can directly stimulate SRIF release, we suggest that GRF causes a receptor-mediated increase in the metabolism of phosphatidylinositol and cGMP formation. These actions therefore may be among the early metabolic events in the mechanism of GRF-stimulated SRIF release from the ME.
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PMID:Rat growth hormone-releasing factor stimulates cyclic GMP formation and phosphatidylinositol metabolism in the median eminence. 167 56

The aim of this study was to characterize the effects of prolonged infusion of growth hormone-releasing factor (1-29)NH2 (GRF) on plasma concentrations of hormones and metabolites when administered to control pigs and pigs immunized against somatostatin (SRIF). In the first experiment, eight purebred Yorkshire boars averaging 113 +/- 2 kg BW were immunized against SRIF conjugated to bovine serum albumin (BSA) (n = 4) or BSA alone (n = 4). Somatotropin (ST) response to four rates of GRF infusion (0, 1.66, 5 and 15 ng/min/kg BW) for 6 hr was evaluated using a double balanced 4 x 4 Latin square design. During the 4 hr before infusion, SRIF-immunized animals tended (P = 0.06) to have a higher ST release (613 vs 316 ng.min/ml, SE = 232) than controls. During infusion, GRF elicited a dose-dependent increase in ST release in both squares; the ST response was not better in SRIF-immunized animals than in controls (P greater than 0.05) (1435 vs 880 ng.min/ml; SE = 597). In the second experiment, ten purebred Yorkshire boars (5 controls and 5 SRIF-immunized animals) averaging 69 +/- 2 kg BW were continuously infused with GRF at the rate of 15 ng/min/kg BW for six consecutive d. Under GRF infusion, ST concentrations increased (P less than 0.05) from 805 to 4768 ng.min/ml (SE = 507) from day 1 to day 6 in both SRIF-immunized and control animals. Prolactin levels increased (P less than 0.05) with GRF infusion; pattern of increase was different (P less than .01) overtime in control and SRIF-immunized animals. Thyroxine levels increased from 2.53 to 3.45 micrograms/dl (SE = 0.16) after six d of infusion. Insulin-like growth factor I was higher (P less than 0.05) before (139 vs 90 ng/ml; SE = 11) and during (222 vs 185 ng/ml; SE = 11) GRF infusion in SRIF-immunized animals. A transient increase (P less than 0.05) in glucose and insulin was observed in both groups. Immunization against SRIF had no effect on blood metabolites; however, GRF infusion increased free fatty acids from 157 to 204 microEq/l (SE = 11) and decreased blood urea nitrogen from 4.1 to 3.5 mmol/l (SE = 0.2) from day 1 to day 6, respectively. In summary, active immunization against SRIF in growing pigs increased ST and IGF-I concentrations. Infusion of GRF continuously raised ST levels with days of infusion without any sign of decrease responsiveness.
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PMID:Effect of growth hormone-releasing factor infusion on somatotropin, prolactin, thyroxine, insulin, insulin-like growth factor I and blood metabolites in control and somatostatin-immunized growing pigs. 167 61

The aim of this study was to investigate the interrelationships between alpha 2-adrenergic and cholinergic pathways in the control of hypothalamic somatostatin (SRIF) secretion in humans. In eight normal volunteers subjects we compared the pattern of GHRH-induced GH release to that elicited by similar challenge given 60 min after a pretreatment with drugs affecting alpha 2-adrenergic and muscarinic cholinergic neurotransmission. In a control study, synthetic GHRH [GRF-(1-29); 1 microgram/kg, iv] was administered 60 min after giving placebo. In other experiments, the administration of atropine (1 mg, im), or clonidine (0.300 mg, orally), or atropine plus clonidine, or pyridostigmine (120 mg, orally), or yohimbine (30 mg, orally), or pyridostigmine plus yohimbine, at 0 min was followed by GHRH administration 60 min later. The administration of both clonidine and pyridostigmine significantly (P less than 0.01) enhanced the GH responses to GHRH compared to those elicited by this challenge when given after placebo. Conversely, atropine pretreatment significantly (P less than 0.01) blocked the GH response to GHRH challenge, whereas yohimbine did not significantly affect it. When atropine and clonidine were given together, the inhibitory effect of the former was overcame and mean GHRH-elicited GH peak response was significantly (P less than 0.05) higher than that in the control study. In contrast, pretreatment with yohimbine significantly (P less than 0.05) blunted the pyridostigmine-induced enhancement of GHRH-elicited GH release. These data confirm our previous postulate suggesting that the stimulatory effect of clonidine on GH release is mainly exerted by inhibiting the hypothalamic SRIF release. Moreover, the effect of cholinergic neurons on SRIF release seems to be, at least in part, dependent on alpha 2-adrenergic pathways. Based on these data, it can be proposed that the alpha 2-adrenergic system plays a major role in the control of hypothalamic SRIF release, and hence in GH neuroregulation, whereas the muscarinic cholinergic system would participate in such regulation by modulating the functional activity of the former.
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PMID:Evidence that alpha 2-adrenergic pathways play a major role in growth hormone (GH) neuroregulation: alpha 2-adrenergic agonism counteracts the inhibitory effect of muscarinic cholinergic receptor blockade on the GH response to GH-releasing hormone, while alpha 2-adrenergic blockade diminishes the potentiating effect of increased cholinergic tone on such stimulation in normal men. 167 61

The effects of hypothyroidism duration on several factors implicated in GH secretion control were studied in the male rat at different maturity stages, ranging from the peripuberal period to adulthood. Thyroid ablation was performed on 22-day-old Wistar male rats maintained on a low iodine diet (T group). Age-paired controls (C group) were fed with the same diet, supplemented with potassium iodide. Subgroups of T and C animals (aged 32, 42, 52, 82 and 112 days) were studied 10, 20, 30, 60 and 90 days after surgery. After pentobarbital anesthesia, jugular blood was withdrawn before and 5 min after an intravenous TRH stimulus, for GH assay. Hypothalamic and pituitary tissues were obtained in order to measure GH, immunoreactive somatostatin (IR-SRIF) and growth hormone-releasing factor (IR-GRF). Growth rate and serum testosterone confirmed that C rats reached sexual maturity by day 30 of the study. Mean +/- SE serum GH (ng/ml) increased (p less than 0.05) in C animals from day 10 (38.5 +/- 5) to day 30 (67.4 +/- 7.3), with no significant variations thereafter. The same time sequence pattern was observed in pituitary GH concentrations. In T rats, both serum and pituitary GH decreased progressively from day 10 to 90, being significantly lower than in C at all times of the study. No GH response to TRH could be found in C groups. In contrast, GH increased significantly (p less than 0.05) in T animals after TRH at days 20 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of hypothyroidism duration on developmental changes in the hypothalamic factors implicated in growth hormone secretion in the male rat. 168 42

To determine whether galanin (GAL), a 29-amino acid neuropeptide, plays a role in the physiological regulation of the pulsatile secretion of GH and PRL in the male rat, secretory patterns of both hormones were studied in freely moving animals after GAL passive immunoneutralization. Adult male Sprague-Dawley rats were equipped with iv and intracerebroventricular catheters. After 7 days, 3 microliters of a specific GAL antiserum (GAL-AS) or normal rabbit serum (NRS; controls) were infused in the third ventricle of 10 rats, 25 and 1 h before the animals were bled every 15 min for 6 h (1000-1600 h). Plasma GH and PRL concentrations were measured by RIA, and the hormonal secretory patterns were analyzed by the PULSAR program. Control rats, treated with NRS, displayed typical GH secretion, with pulses of high amplitude (167 +/- 27 ng/ml) and low frequency (2.4 +/- 0.2 pulses/6 h), separated by periods of low trough levels (3.8 +/- 0.6 ng/ml). Rats treated with GAL-AS had altered pulsatile GH secretion. Pulse height was markedly reduced (77 +/- 15 ng/ml; P less than 0.01 vs. controls), and peak frequency was higher (3.6 +/- 0.5 pulses/6 h; P less than 0.05), while GH baseline levels and integrated GH secretion over the 6-h sampling period remained unaltered. Injection of rat GH-releasing hormone (1 microgram/rat, iv) caused a similar GH stimulation in both groups of rats, as determined by the peak GH response at 5 min (368 +/- 112 vs. 342 +/- 81 ng/ml) or by the integrated GH response over 1 h (5.13 +/- 1.30 vs. 4.77 +/- 1.15 micrograms.min/ml in NRS- and GAL-AS-treated rats, respectively; P less than 0.05). In contrast to GH, pulsatile secretion of PRL was not affected by the GAL-AS treatment. These results indicate that GAL is a physiological regulator of spontaneous pulsatile secretion of GH, but not PRL, in the male rat. The influence of GAL on GH secretion appears to be exerted within the hypothalamus, mainly by a stimulation of GRF secretion. However, the changes in GH pulse frequency observed after GAL immunoneutralization suggest that GAL might also influence the somatostatin inhibitory tone.
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PMID:Galanin is a physiological regulator of spontaneous pulsatile secretion of growth hormone in the male rat. 168 91

Lactotrophs, somatotrophs, and thyrotrophs have been shown to contain immunoreactive galanin. Furthermore, estrogen stimulates galanin mRNA and peptide levels in the rat anterior pituitary, particularly within lactotrophs. To determine whether galanin is released from the anterior pituitary in a regulated manner, we used cultured pituitary cells from male and ovariectomized Fischer 344 rats implanted with estrogen-containing capsules. Anterior pituitary cells (5 x 10(5) cells/well) were challenged (0.5-3 h) with hypothalamic factors known to regulate anterior pituitary hormone secretion, and medium galanin levels were measured by RIA. In female pituitary cells, galanin secretion was inhibited by dopamine (10 and 100 nM) and stimulated by TRH (20 and 100 nM). Although galanin release was significantly lower in male pituitary cells, dopamine and TRH inhibited and stimulated galanin secretion, respectively. Medium galanin levels were also significantly reduced by somatostatin (5 nM) in both female and male cells. The pattern of PRL release in response to dopamine, TRH, and somatostatin was similar to that observed for galanin, regardless of the sex of the pituitary donor. Although galanin has been localized in somatotrophs, 5 nM GH-releasing hormone (GRF) failed to alter galanin release in male as well as female pituitary cells; GH secretion was significantly increased by GRF. LHRH (5 nM) and CRF (5 nM) failed to alter galanin release in vitro. We conclude that in estrogen-exposed pituitary cells obtained from male and ovariectomized Fischer 344 rats: 1) galanin secretion is inhibited by dopamine and somatostatin, and stimulated by TRH; 2) GRF, LHRH, and CRF do not regulate galanin release in these cells; and 3) the profile of the regulated pathway for galanin release suggests that the primary location of galanin is the lactotroph, probably within secretory granules.
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PMID:Galanin secretion from anterior pituitary cells in vitro is regulated by dopamine, somatostatin, and thyrotropin-releasing hormone. 170 85

Somatostatin (SRIF) reduces growth hormone releasing hormone (GRF)-stimulated growth hormone (GH) release from avian and mammalian adenohypophyseal cells. The present studies examined the intracellular mechanisms mediating SRIF inhibition of GRF-stimulated GH release from chicken pituitary cells. Increases (P less than 0.05) in GH release were observed in the presence of (1) GRF; (2) the adenylyl cyclase stimulator, forskolin; (3) a cAMP analog, 8-bromo-cAMP; (4) the phosphodiesterase inhibitor 3-isobutyl-l-methyl-xanthine (IBMX) combined with GRF; (5) a tumor-promoting phorbol ester and protein kinase C activator, phorbol 12-myristate, 13-acetate (PMA); (6) a diacylglycerol analog, 1,2-dioctanoyl-glycerol (DiC8); and (7) a calcium ionophore, A23187, alone and in combination with PMA. Somatostatin (10 ng/ml) reduced the release of GH stimulated by GRF, forskolin, and 8-bromo cAMP and the GRF-provoked release of GH in the presence of IBMX (P less than 0.05). Somatostatin, however, did not influence GH release in the presence of the protein kinase C activators, PMA or DiC8, or the calcium ionophore A23187. These data suggest that SRIF inhibits GRF-provoked GH release by reducing the ability of the cAMP-protein kinase A but not of the calcium or protein kinase C intracellular message pathways to stimulate GH release.
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PMID:Possible involvement of adenylyl cyclase-cAMP-protein kinase a pathway in somatostatin inhibition of growth hormone release from chicken pituitary cells. 170 26

The large availability of biosynthetic GH suggested the need to define the more accurate way to make diagnosis of GH deficit. Only one stimulation test by clonidine or insulin is not enough to define a GH deficit, and this because often it's possible to get "false negative" tests. The GH is regulated by the influence of GRF and somatostatin that respectively are under the adrenergic and cholinergic control, for this reason we studied how and in which measure a cholinergic agonist (pyridostigmine) acts on GH release during the clonidine and GRF stimulation tests. We studied the area under the curve (AUC), the peak and the mean of the value of GH after clonidine or clonidine and pyridostigmine, and after GRF or GRF and pyridostigmine: we got the following results: 191 +/- 71.33 (AUC), 5.42 +/- 1.68 (peak), 2.44 +/- 0.54 (mean) after clonidine stimulation test; 1048 +/- 442.37 (AUC), 19.5 +/- 10.15 (peak) and 7.96 +/- 3.2 (mean) after clonidine and pyridostigmine (p less than 0.01); 1499 +/- 887 (AUC), 21.1 +/- 11.8 (peak) and 11.11 +/- 6.6 (mean) after GRF test and 2370 +/- 332 (AUC), 31.4 +/- 3.49 (peak) and 18.22 +/- 3.27 (mean) after GRF and pyridostigmine. The pyridostigmine effect on the simulation by clonidine and GRF is able to potentiate the stimulation of GH and allowed a more accurate diagnosis of GH deficit.
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PMID:[Effect of pre-treatment with pyridostigmine on the stimulation of growth hormone by clonidine and GRF]. 175 82

A number of in vivo studies suggest that hypothalamic somatostatin (SRIF) tone is stimulated by the beta-adrenergic system. Employing dispersed adult male rat hypothalamic cells, we studied the effects of beta-adrenergic antagonists on the release of hypothalamic SRIF. Propranolol, at concentrations of 1-100 microM, had no detectable effect on basal SRIF release, but caused dose-dependent inhibition of SRIF release stimulated by ouabain. Two other beta-adrenergic antagonists, labetolol and metoprolol, also caused inhibition of ouabain-stimulated SRIF release. The alpha 2-agonist clonidine was without effect on SRIF release under basal or stimulated conditions. GH secretion from monolayers of dispersed rat anterior pituitary cells was also examined. Propranolol (1-100 microM) had no significant effect on basal GH secretion or GH secretion stimulated by rat GRF. In conclusion, 1) beta-adrenergic antagonists caused inhibition of stimulated SRIF release; 2) clonidine had no detectable effect on SRIF release; and 3) propranolol did not affect GH secretion in vitro. These findings support the hypothesis that beta-adrenergic antagonists augment GH responsivity by inhibiting hypothalamic SRIF release.
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PMID:Inhibition of hypothalamic somatostatin release by beta-adrenergic antagonists. 196 76

To investigate possible sex differences in the feedback regulation of growth hormone (GH) secretion, concentrations of immunoreactive GH-releasing hormone (GRF) and somatostatin (SS) were measured in the median eminence (ME) and the hypothalamus of male and female rats bearing the MtTW15 tumor, which secretes high amounts of GH and prolactin (PRL). Four weeks after tumor implantation in male rats, the GRF concentration in the whole hypothalamus, including the ME, was decreased by 37% (0.29 +/- 0.02 vs. 0.46 +/- 0.02 ng/mg protein in intact male controls; p less than 0.001) and the concentration of SS was increased by 40% (11.5 +/- 0.7 vs. 8.1 +/- 0.3 ng/mg protein in male controls; p less than 0.01). In female rats, the presence of tumor for 4 weeks caused a smaller (18%) reduction in GRF concentrations (0.27 +/- 0.02 vs. 0.33 +/- 0.03 ng/mg protein in intact female controls; p less than 0.05) and no significant change in SS concentrations (10.2 +/- 0.08 vs. 9.7 +/- 0.8 ng/mg protein in female controls). Tumor-related changes in GRF and SS concentrations were also more pronounced in male rats than in females, when determined separately in the microdissected ME and in the remaining hypothalamus. These differences occurred despite similar increases in serum GH, PRL and insulin-like growth factor I concentrations in male and female tumor-bearing rats. To assess which hormone (GH or PRL) was responsible for these changes, intact male rats were treated for 10 days with 2 daily s.c. injections of rat GH (rGH; 100 and 250 micrograms/day), rat PRL (100 and 250 micrograms/day) or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sexual differentiation of growth hormone feedback effects on hypothalamic growth hormone-releasing hormone and somatostatin. 196 35


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