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)

We have evaluated the effect of the administration of galanin (Gal), a newly identified hypothalamic peptide, on baseline and GHRH-induced GH rise in five obese children and in seven controls. The GH response to GHRH (hpGRF(1-29), 1 microgram/kg i.v.), and to Gal (15 micrograms/kg/h for 1 h), evaluated both as the maximum GH peak and as integrated area under the curve (AUC), was significantly lower in the obese children than in the controls. Simultaneous administration of Gal plus GHRH significantly increased the GH response to GHRH in all the obese subjects, so that their mean peak GH levels and AUC after Gal plus GHRH were similar to those of the control children after GHRH. Also, in control children Gal caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean AUC after Gal plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Our data indicate that obese children have a blunted GH response to Gal, which, however, is able to enhance the GH response to GHRH. This observation strengthens the view that the mechanism of action of Gal involves modulation of endogenous somatostatin (SRIH) release. In addition, similarity between the effects of Gal and pyridostigmine on baseline and GHRH-stimulated GH release in obese children may indicate the existence of a cholinergic link in the action of Gal.
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PMID:The effect of galanin on baseline and GHRH-induced growth hormone secretion in obese children. 169 89

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 effects of the peptide galanin on growth hormone secretion were studied in vitro using cultured rat and human anterior pituitary cells, and in vivo by iv administration of galanin in both rats and humans. Galanin in concentrations from 10 nmol/l to 1 mumol/l did not alter basal GH release, but slightly inhibited GHRH-stimulated GH release from cultured rat anterior pituitary cells. Galanin (1 mumol/l) did not significantly change basal or GHRH-stimulated GH secretion from cultured human anterior pituitary cells. In contrast, iv injection of 1 microgram (300 pmol) galanin to rats induced an increase in plasma GH that was reproducible at repetitive injections. The galanin-induced GH release in rats was of a lower magnitude than the increase in plasma GH after iv injections of GHRH, and was seen with a 5-15 min delay in comparison to iv administered GHRH. In man, iv infusions of galanin (40 pmol.kg-1.min-1.(40 min)) also caused a significant increase in plasma GH, but it occurred 25-30 min after the beginning of the infusion. These results suggest an indirect action of galanin on GH release in both rats and humans, i.e. galanin does not directly affect the somatotropes. In agreement with a central action, no binding sites for galanin could be demonstrated in the rat anterior pituitary by autoradiography. Since galanin did not affect somatostatin release from fragments of rat mediobasal hypothalamus, the stimulatory effects of galanin on GH release are most likely mediated via a stimulatory effect on GHRH neurons.
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PMID:On the role of the peptide galanin in regulation of growth hormone secretion. 172 67

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 transgene rabbit with the human growth hormone releasing factor gene was produced by a method of microinjections into fertilized oocytes; a mouse metallothionein I gene was used as a promoter. Gene expression was accompanied by a phenotypical effect, expressed in increasing the rates of development. The maximum difference among the transformant, transplants and control was revealed on the 30-45th day of postnatal development. Analysis of the hormonal status of the transgene animal has shown change in the levels of the majority of hormones: a 6-10-fold increase in insulin; a 2-3-fold increase in the level of triiodothyronine, thyroxin; a reduced somatostatin concentration, a two-fold decrease in the level of progesterone, and a four-fold decrease in the level of testosterone. Activation of the promoter zone with Zn++ salts for 5 weeks resulted in a further increase in the transformant body mass by 10%. However blood hormone levels in the transgene rabbit returned to normal. Proceeding from the above it can be assumed that exogenous gene expression probably increased somatotropin secretion which determined dysfunction of most of the endocrine glands; the effect of somatotropin was probably insulin-mediated.
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PMID:[Influence of the expression of the human growth hormone releasing factor gene on hormone levels in a transgenic rabbit]. 178 15

GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), a hexapeptide derived from enkephalin, has been shown to have GH-releasing activity in man and several animal species. To characterize the GHRP dose-response curve and compare it with that of GH-releasing hormone [GHRH-(1-44)NH2], six unanesthetized young adult cynomolgus macaques were tested with a range of iv doses of GHRP or GHRH in random order. Animals were fitted with vests and tethers. Blood samples were obtained before and at 15-min intervals after the administration of drugs. Doses ranged from 0.03-3 mg/kg for GHRP and from 1-30 micrograms/kg for GHRH. The dose-response curves for the two peptides were not parallel. GHRP had lower potency, but evoked a much higher peak GH response than GHRH (greater than 55 vs. 12 micrograms/L). Because one of the proposed mechanisms of action of GHRP is the inhibition of somatostatin (SS), we tested the effects of propranolol, which inhibits SS, on the GH responses to GHRH and GHRP. Propranolol was given at a dose of 14 micrograms/kg, iv, 10 min before the injection of saline, GHRH (10 micrograms/kg), or GHRP (1 mg/kg). GH responses to propranolol alone did not differ from those to placebo (peak, 6 +/- 2 vs. 8 +/- 2 micrograms/L). However, propranolol pretreatment doubled the GH responses to both GHRH and GHRP compared with those to GHRH or GHRP alone 28 +/- 5 micrograms/L vs. 14 +/- 5 (P less than 0.05) and 54 +/- 2 vs. 25 +/- 6 micrograms/L (P less than 0.001), respectively]. These results show that GHRP causes a potent dose-dependent release of GH in this primate species. Since GHRP can produce a greater maximal GH response than GHRH, mechanisms other than release of endogenous GHRH must be involved.
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PMID:Growth hormone (GH) responses to the hexapeptide GH-releasing peptide and GH-releasing hormone (GHRH) in the cynomolgus macaque: evidence for non-GHRH-mediated responses. 185 62

Growth hormone-releasing hormone (GHRH) stimulates GH secretion in man and the hormonal response is specific. The attenuation of GH response to bolus GHRH after prior exposure of GHRH of up to 24 h was not demonstrated in normal or GH-deficient subjects after more prolonged exposure. This suggests that the partial loss of responsiveness to GHRH may reflect short-term negative feedback by GH. The stimulatory effect of clonidine and L-dopa on GH release is mediated via GHRH. Other stimuli like hypoglycaemia, arginine and propranolol augment GH release in man by modulating hypothalamic somatostatin secretion. Although GHRH test can differentiate between hypothalamic or pituitary cause of GH deficiency, it is of little diagnostic value in children with short stature. Favourable results have been observed in 60-70% of GH-deficient children treated with GHRH, but the dose and mode of administration are still being explored. We found that low dose (1-2 micrograms/kg) GHRH given subcutaneously every 3 h by a pump was effective in promoting growth in 5 of 7 patients after 1 year. Treatment was continued for 2-4 years in 4 patients and growth velocities ranging from 4.5 to 8.2 cm/year were maintained using a dose of 3 micrograms/kg/pulse.
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PMID:Growth hormone-releasing hormone: clinical studies and therapeutic aspects. 190 90

Sex steroids contribute to modulate GH secretion in man. However, both the exact locus and mechanism by which their actions are exerted still remain not clearly understood. We undertook a number of studies designed to ascertain: (1) whether or not sudden or chronic changes in circulating gonadal steroids may affect GH secretion in normal adults; and (2) the reason(s) for gender-related dimorphic pattern of GH release. The pituitary reserve of GH, as evaluated by means of a GHRH challenge, was similar in women with anorexia nervosa and in normally menstruating women. Estrogenic receptor blockade with tamoxifen (TMX) did not significantly change GHRH-induced GH response in these normal women. Therefore, acute or chronic hypoestrogenism apparently had no important effects at level of somatotrophs. In another group of normal women we tested the possibility that changes in circulating estrogens might induce changes in the hypothalamic-somatotroph rhythm (HSR). GHRH challenges were performed throughout a menstrual cycle, and again after having achieved functional ovarian blockade with a GnRH agonist treatment. Short-term ovarian blockade did not significantly affect the parameters of GH response to GHRH, although it was accompanied by an increase in the number of women in a refractory HSR phase at testing. This suggested a low potentiating effect on the basic pattern of somatostatin (SS) release occurring as a consequence of the decrease in circulating estrogens. In normal men, neither the GH response to GHRH nor the HSR were affected by functional testicular blockade (after GnRH agonist treatment). However, the administration of testosterone enanthate (250 mg) to another group of men increased both the GHRH-induced GH release and the number of subjects in a spontaneous secretory HSR phase at testing; these were reversed by estrogenic receptor blockade with TMS. In another group of normal men, the fraction of GH secreted in pulses (FGHP) during a nocturnal sampling period was significantly decreased by testicular blockade. Other parameters of GH secretion,such as the number of GH pulses and their mean amplitude (A), and the mean plasma GH concentration (MCGH), showed a slight, although not significant, decrease following the lack of androgens. The administration of testosterone enanthate (500 mg) reversed these parameters to values similar to those in the basal study. Interestingly, when tamoxifen was given after testosterone enanthate, A, MCGH and FGHP increased to values significantly higher than in any other experimental condition in that study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of sexual steroids in the modulation of growth hormone (GH) secretion in humans. 195 17

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


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