Hypothalamic Somatostatin Gene Expression Research Articles

Endotoxin administration increases hypothalamic somatostatin mRNA through nitric oxide release

Acute inflammation induced by endotoxin (LPS) administration inhibits insulin-like growth factor (IGF-I) and growth hormone (GH) secretion. The aim of this study was to elucidate the role of glucocorticoids and nitric oxide (NO) in the effect of LPS on hypothalamic somatostatin gene expression. Adult male Wistar rats were injected with different doses of LPS (5, 10 and 100 μg/kg). Rats received two i.p. injections of LPS (at 17:30 and 8:30 h the following day) and were killed 4 h after the second injection. LPS administration at the dose of 100 μg/kg increased the hypothalamic somatostatin mRNA content, as well as the serum concentrations of corticosterone. Glucocorticoids do not seem to be involved in LPS-induced increase in hypothalamic somatostatin mRNA since adrenalectomy did not prevent this effect. In order to analyze the possible effect of NO, aminoguanidine, an inducible nitric oxide synthase inhibitor, was injected (100 mg/kg s.c.) simultaneously with LPS injection. Aminoguanidine administration did not modify somatostatin mRNA in saline injected rats, but it prevented LPS-induced increase in hypothalamic somatostatin mRNA. These data suggest that the stimulatory effect of endotoxin on hypothalamic somatostatin gene expression is not mediated by glucocorticoids, but instead by the increase in NO release.

Effects of intrauterine and early postnatal growth restriction on hypothalamic somatostatin gene expression in the rat.

In the human, intrauterine growth retardation (IUGR) can result in persistent postnatal growth failure, which may be attributable, in part, to abnormal GH secretion. Whether putative alterations in GH secretion are the result of abnormalities intrinsic to the pituitary or reflect changes in the production of GH-releasing hormone or somatostatin (SS) is unknown. We tested the hypothesis that growth failure associated with IUGR or early postnatal food restriction (FR) is caused by a central defect in hypothalamic SS gene expression. Both models displayed persistent growth failure postnatally without any catch-up growth. We measured levels of SS mRNA levels in rats experimentally subjected to IUGR or FR. SS mRNA levels were measured by semiquantitative in situ hybridization throughout development. Levels of SS mRNA in the periventricular nucleus were significantly higher in both male and female IUGR rats in the juvenile and adult stages compared with matched controls (p < or = 0.05). FR was associated with higher SS mRNA levels only in neonatal female rats (p < or = 0.05). These results suggest that intrauterine malnutrition induces a persistent increase in the expression of SS mRNA in the periventricular nucleus, whereas early postnatal FR results in only a transient increase in SS gene expression. Because IGF-I levels were normal in juvenile IUGR and FR rats, central dysregulation of SS neurons does not appear to be the cause of early postnatal growth failure in either model. However, these observations are consistent with the hypothesis that nutritional stress at critical times during development can have persistent and potentially irreversible effects on organ function.

Dexamethasone decreases somatostatin mRNA levels in the periventricular nucleus of the rat hypothalamus.

Glucocorticoid excess inhibits somatic growth in man and laboratory animals. While the mechanism involved is likely to be multifactorial, indirect evidence suggesting the role of an enhanced endogenous somatostatin (SS) tone has been reported. However, there has been no direct evidence indicating an increased synthesis or secretion of hypothalamic SS. In this study, we investigated the effects of glucocorticoids on hypothalamic SS expression by measuring the peptide and mRNA content of SS in whole hypothalamic blocks of male Sprague-Dawley rats sacrificed 4 weeks after adrenalectomy or sham operation. Adrenalectomy decreased the SS content in the rat hypothalamus (p < 0.05), an effect which was reversed by dexamethasone treatment for 10 days. On the other hand, total hypothalamic SS mRNA levels were unaffected by adrenalectomy, but became significantly decreased following dexamethasone treatment (p < 0.05). Using in situ hybridization, this reduction in SS gene expression was shown to occur consistently in the periventricular nucleus and in the parvocellular subdivision of the paraventricular nucleus. The effects of adrenalectomy and dexamethasone on SS mRNA levels were further quantitated in hypothalamic fragments containing predominantly the periventricular and paraventricular nuclei. Somatostatin mRNA levels in these tissue fragments were marginally increased by adrenalectomy (p < 0.05), but showed a 50% reduction following dexamethasone treatment (p < 0.0001). In conclusion, our findings suggest that the inhibitory effect of glucocorticoids on somatic growth is probably not mediated via an effect on hypothalamic SS gene expression.