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 persiste nt postnatal growth failure, which may be attributable, in part, to abnorma l GI-I secretion. Whether putative alterations in GI-I secretion are the re sult of abnormalities intrinsic to the pituitary or reflect changes in the production of GH-releasing hormone or somatostatin (SS) is unknown. We test ed the hypothesis that growth failure associated with IUGR or early postnat al food restriction (FR) is caused by a central defect in hypothalamic SS g ene 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 sem iquantitative ir? situ hybridization throughout development. Levels of SS m RNA in the periventricular nucleus were significantly higher in both male a nd female IUGR rats in the juvenile and adult stages compared with matched controls (p less than or equal to 0.05). FR was associated, with higher SS mRNA levels only in neonatal female rats (p less than or equal to 0.05), Th ese results suggest that intrauterine malnutrition induces a persistent inc rease in the expression of SS mRNA in the periventricular nucleus, whereas early postnatal FR results in only a transient increase in SS gene expressi on. 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 postna tal growth failure in either model. However, these observations are consist ent with the hypothesis that nutritional stress at critical times during de velopment can have persistent and potentially irreversible effects on organ function.