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)

Growth hormone receptor (GHR) mRNA-expressing cells in the hypothalamus were observed using hybridization histochemistry in adult male rats. Digoxigenin-labeled cRNA corresponding to the extracellular part of rat GHR was used as a probe. Northern blotting analysis of hypothalamic total RNA from adult male rats revealed that the 4.5 kilobase (kb) transcript of the GHR gene corresponding to the GHR messenger RNA (mRNA) predominated over the 1.2 kb transcript corresponding to GH-binding protein mRNA. GHR mRNA-containing cells were observed in the arcuate nucleus (ARC), the periventricular nucleus (PeV), ventrolateral region of the ventromedial nucleus, the paraventricular nucleus and the supraoptic nucleus. To further understand the significance of the GHR gene expression in the hypothalamus, the effect of in vivo manipulation of GH on the somatostatin (SS) gene expression in the ARC and PeV, and the GRF gene expression in the ARC was observed among adult male rats using in situ hybridization histochemistry. Ten days after hypophysectomy, the SS mRNA level in the ARC as well as PeV was significantly lower than that in the respective nuclei of sham-operated control rats, while the GRF mRNA level in the ARC was significantly higher than that in the ARC of control animals. Subcutaneous injection of recombinant human GH (0.33 mg) to hypophysectomized rats every 12 h for 5 days restored the SS mRNA level in the ARC and PeV, and reduced the GRF mRNA level in the ARC to that of control animals. The data suggest that GH directly acts on the hypothalamic PeV and ARC, and alters the gene expression of SS and GRF.
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PMID:Expression of growth hormone receptor gene in rat hypothalamus. 868 Apr 43

Somatostatin has been suggested to influence the somatotrophic axis outside the central nervous system, in reducing GH-induced IGF-I mRNA and IGF-I generation. This study aimed to determine whether such effects were mediated via the GH receptor (GHR). GH-deficient dwarf rats aged 45-47 days (n = 8 per group) received twice daily subcutaneous injections of octreotide (1 mg/kg) (group O), saline (group S), octreotide (1 mg/kg) plus bovine GH (0.25 mg/kg) (group OG), or bovine GH (0.25 mg/kg) plus saline (group G) for 10 days. Octreotide-treated animals had less weight gain compared with saline-treated animals, but not when GH cotreated (group OG vs G). Octreotide had an overall effect on decreasing length gain (P < 0.01). Serum IGF-I (ng/ml) was reduced by octreotide (group O 171 +/- 11, group S 239 +/- 20, P < 0.01; group OG 283 +/- 30, group G 362 +/- 10, P < 0.001), as was serum insulin (P < 0.001). A significant decrease in hepatic and muscle IGF-I mRNA expression was found as expected, yet this was not associated with decreased hepatic GHR expression. Rather, an increase in hepatic 125I-bovine GH specific binding was observed (P < 0.001) and, in GH-cotreated animals (OG), hepatic GHR and GH binding protein (GHBP) mRNA expression were also increased by octreotide by approximately 40%. In muscle, octreotide was associated with an approximately 30% decrease in GHBP mRNA and no effect on GHR mRNA. This study suggests that the suppressive effects of octreotide on IGF-I metabolism, at least in liver, are not mediated via down-regulation of GHR expression, but more likely by direct effects on IGF-I expression.
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PMID:The effects of octreotide on GH receptor and IGF-I expression in the GH-deficient rat. 870 33

GH receptor (GHR) expression differs during development between central and peripheral tissues. Peripheral GHR expression is known to be sensitive to gonadal and adrenal steroids, but little is known about their effects on GHR in the central nervous system. We have now studied the effects of estradiol (E2) or dexamethasone on GHR expression in rat arcuate nucleus (ARC) and hippocampus, using quantitative in situ hybridization. Dexamethasone, which strongly down-regulates hepatic GHR expression, had no effect on central GHR transcript abundance, whereas E2 treatment, which stimulates hepatic GHR expression, significantly reduced ARC GHR messenger RNA (mRNA) levels. E2 also increased somatostatin (SS) expression significantly in both ARC and periventricular nuclei but did not reduce ARC GH-releasing hormone (GHRH) mRNA levels. Ovariectomy stimulated GHR and GHRH mRNA levels in the ARC, whereas it lowered ARC SS expression. E2 replacement in ovariectomized animals restored GHRH and SS mRNA levels to control values. Hippocampal GHR mRNA transcripts showed the same response to these endocrine manipulations as seen in the ARC. The induction of hepatic GHR expression by E2 is known to involve the transcription of an alternate 5' untranslated first exon, GHR1. This was readily detectable in the liver using a specific GHR1 probe but could not be detected in any CNS area. Our results show that GHR expression in the CNS is sensitive to regulation by peripheral steroids but that CNS and hepatic expression of GHR is differentially regulated by the same treatments.
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PMID:Differential regulation of the growth hormone receptor gene: effects of dexamethasone and estradiol. 875 62

The neuroendocrine regulation of pulsatile growth hormone (GH) secretion involves the reciprocal interactions between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurones, residing primarily in the hypothalamic arcuate nucleus (ARC) and the periventricular nucleus (PeN), respectively. Considerable evidence supports the concept that GH itself participates in the regulation of its own rhythmic secretion through a reciprocal feedback on GHRH and somatostatin neurones. The direct actions of GH are mediated through GH receptors, and in the PeN, the majority of somatostatin neurones express this receptor. GH induces the expression of the immediate early gene c-fos in the ARC; however, few GHRH residing in the ARC express the GH receptor, suggesting that the action of GH on GHRH cells must be indirect through another population of unidentified cells. NPY neurones express c-fos in response to GH, and preliminary results suggest that NPY neurones in the ARC express the GH receptor. These observations suggest that NPY neurones play a physiological role in the feedback of regulation of GH secretion.
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PMID:Role of NPY neurones in GH-dependent feedback signalling to the brain. 880 21

Elevated glucocorticoid (GC) levels produce a marked impairment in somatic growth in both rodents and primates. In addition, GC play an important role in the regulation of growth hormone (GH) synthesis and secretion. Blunted GH response to stimulation tests in conditions of chronic exposure to excessive cortisol secretion or administration are well documented. In contrast, acute administration of GC to normal human subjects induces a transient increase in plasma GH levels. This dual action of GC on GH secretion is probably due to the fact that they act at different loci; i.e. in the regulation of GH transcription and GHRH and somatostatin receptors at the pituitary level as well as GHRH, somatostatin and GH receptor gene expression at the hypothalamic level.
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PMID:Role of glucocorticoids in the neuroregulation of growth hormone secretion. 888 68

Although it is well known that chronic treatment with glucocorticoids inhibits somatic growth, the mechanism of action of this inhibitory effect is not completely understood. It is likely that glucocorticoids act at various levels, including pituitary, hypothalamus, and peripheral organs modulating GH synthesis, secretion, and action. In this work, we evaluated the effect of dexamethasone on hypothalamic somatostatin and GH-releasing hormone (GHRH) messenger RNA (mRNA) levels by in situ hybridization. We found a significant decrease of somatostatin mRNA content in the periventricular nucleus of the hypothalamus after 3, 8, and 15 days of treatment with dexamethasone. Furthermore, we observed a reduction in GHRH mRNA levels in the arcuate nucleus after 8 and 15 days of treatment with this steroid. As it has been shown that GH feeds back to regulate somatostatin and GHRH expression at the hypothalamic level through high affinity GH receptors, we evaluated the possibility of a GH-mediated action in the inhibitory effect of glucocorticoids on somatostatin and GHRH mRNA levels. To address this issue, we first studied the GH receptor mRNA content in both the periventricular and arcuate nuclei of the hypothalamus after dexamethasone treatment. Secondly, the effect of dexamethasone on somatostatin and GHRH mRNA levels in hypophysectomized animals also was assessed. We found a significant decrease in GH receptor mRNA levels in the periventricular nucleus and in the arcuate nucleus after 1, 3, 8, and 15 days of glucocorticoid administration. Finally, in hypophysectomized rats, dexamethasone treatment for 15 days did not reduce somatostatin mRNA levels in the periventricular nucleus but significantly decreased GHRH mRNA content in the arcuate nucleus. In summary, our results suggest an inhibitory GH-mediated effect of dexamethasone on somatostatin mRNA levels in the periventricular nucleus and an inhibitory direct effect of dexamethasone on GHRH neurones in the arcuate nucleus.
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PMID:Regulation of hypothalamic somatostatin, growth hormone-releasing hormone, and growth hormone receptor messenger ribonucleic acid by glucocorticoids. 894 Mar 40

It has been surmised that GH exerts feedback action on the hypothalamus and thereby regulates its own secretion. Our previous studies suggested that GH acts on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However, there remains uncertainty whether GH acts directly or indirectly through the generation of IGFs on the hypothalamus to regulate its own secretion. To examine this, rat GH (rGH) or human IGF-I was injected directly into a defined area of the hypothalamus, and the blood GH profile was observed in conscious male rats. In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion was inhibited, and the inhibition lasted for 12 h. During the period of inhibition, the duration and amplitude of GH pulses were significantly decreased and the episodic secretion of GH appeared irregularly compared with the vehicle-injected control rats. In control rats given the vehicle or those given rGH into the lateral hypothalamus, the blood GH profile did not change and pulsatile GH secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together with the results of our previous studies showing that c-fos gene expression was induced by systemic administration of GH and that GH receptor mRNA was contained in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the present study indicate that GH, but not IGF-I, acts on the cells in the ARC and the PeV or in their vicinity to inhibit its own secretion, presumably by activating the somatostatin and NPY neurons.
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PMID:Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats. 916 18

GH appears to play an important metabolic role during late pregnancy and in lactation maintenance. In this study, pregnant (days 8, 15, and 20 of gestation) and postpartum (days 3 and 8 postpartum, including lactating and nonlactating dams) Wistar rats were used to investigate pituitary GH gene expression and hormone secretion, and the potential alterations of the major signals regulating GH secretion and action [somatostatin (SS) and GH-releasing hormone (GHRH), GH receptor (GH-R), and insulin-like growth factor-I (IGF-I)]. GH and SS messenger RNA (mRNA) were quantitated by Northern blot, and both IGF-I and GH-R mRNA were analyzed by the ribonuclease protection assay technique. Pituitary IR-GH content and GH mRNA increased at midpregnancy. IR-GH content was decreased in lactating rats. Plasma GH levels progressively increased during pregnancy, whereas no significant alterations were shown during lactation. Elevated GH levels persisted during lactation. Levels at this time were higher in nonsuckling compared with suckling dams. Liver GH-R mRNA progressively decreased during pregnancy, but it remained unchanged during lactation. Plasma IGF-I and liver IR-IGF-I constantly decreased during pregnancy, and no significant modifications were seen either in suckling or in nonsuckling animals. IGF-I mRNA accumulation in the liver decreased during pregnancy. After delivery, a progressive decrease of liver IGF-I mRNA occurred. At the hypothalamic level, a progressive increase in the IR-SS content was found during pregnancy, with no SS mRNA modification. After delivery, a higher hypothalamic IR-SS content was found in lactating than in nonlactating rats, with no changes in SS mRNA levels. Hypothalamic IR-IGF-I also showed a progressive increase during pregnancy with no significant alterations during lactation. Hypothalamic IR-GHRH presented a nonsignificant mild increase during pregnancy with no modifications during lactation. In the pituitary, IR-IGF-I content progressively increased during gestation, reaching its highest concentration at day 20. During lactation, pituitary IGF-I did not change. In summary, our data show that the mechanisms of the increase in plasma GH levels occurring during pregnancy include an increase in GH gene expression in the pituitary, a decrease in SS secretion from the hypothalamus, an increase in IR-IGF-I content in the hypothalamus and in the pituitary, and a significant decrease in circulating IGF-I. Plasma and liver IR-IGF-I and IGF-I mRNA in the liver decreased throughout gestation due to a lower GH-R gene expression in the liver. This state of GH resistance with a higher GH/IGF-I ratio could be important in providing supplementary nutrients to the fetus. During lactation, GH and its regulatory machinery did not show important modifications.
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PMID:Regulation of growth hormone (GH) gene expression and secretion during pregnancy and lactation in the rat: role of insulin-like growth factor-I, somatostatin, and GH-releasing hormone. 923 98

Two different dwarf rat models with primary (dw/dw, DW) or secondary (transgenic growth retarded, WF/Tgr) GH deficiency and contrasting hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) expression were implanted sc with GC cells. These form encapsulated rat GH-secreting tumors that maintain high plasma rat GH levels for several weeks. In both strains, GC cell tumors stimulated growth and raised GHBP levels, without affecting pituitary GH content. In DW rats, GC cell implants increased SRIH expression in the periventricular nucleus (PeV), but not in the arcuate nucleus (ARC), whereas their high GHRH expression in ARC was decreased by GC cells. In contrast, GC cell implants in WF/Tgr rats had little effect on the already high SRIH expression in PeV or low GHRH expression in ARC, although they reduced SRIH expression in ARC. GC cell implants also reduced GH receptor expression in both ARC and PeV in the WF/Tgr dwarves. Thus, chronic GH overexposure stimulates rapid growth in both dwarf strains, but has differential hypothalamic effects in these models. This experimental approach now makes it possible to study the effects of pathophysiological concentrations of GH ranging from dwarfism to acromegaly in the same animal model.
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PMID:Intrahypothalamic growth hormone feedback: from dwarfism to acromegaly in the rat. 934 73

The growth hormone (GH) pathway is composed of a series of interdependent genes whose products are required for normal growth (Fig 1). The GH pathway genes include ligands (GH and insulin-like growth factor 1 [lGF-1]), transcription factors (prophet of pit 1, or prop 1 and pit 1), agonists and antagonists (growth hormone-releasing hormone [GHRH] and somatostatin), and receptors (GHRH receptor [GHRHR] and the GH receptor [GHR]). These genes are expressed in different organs and tissues, including the hypothalamus, pituitary, liver, and bone. Effective and regulated expression of the growth hormone pathway is essential for growth in stature as well as homeostasis of carbohydrate, protein, and fat metabolism.
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PMID:Growth disorders caused by genetic defects in the growth hormone pathway. 974 8


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