Somatostatin mRNA Levels within the Periventricular Nucleus Are Regulated by Estradiol and Insulin-like Growth Factor-I in Immature Female Rats

Abstract

Adolescent growth is regulated by developmental increases in growth hormone (GH) secretion. Although the hypothalamic release of GH-releasing hormone (GHRH) stimulates and the release of SRIF inhibits GH secretion, it is not known how these regulatory mechanisms change developmentally. In addition, GH secretion is facilitated during maturation by increases in peripheral estradiol and may be inhibited, via a negative feedback mechanism, by insulin-like growth factor-I (IGF-I). It is not clear whether these act through the hypothalamic regulation of GHRH and somatostatin (SRIF). In order to further understand the regulation of GH secretion during development, the present study determined how estradiol and IGF-I altered SRIF mRNA in the hypothalamus in immature female rats. The working hypotheses were that estradiol would decrease SRIF mRNA accounting, in part, for its positive effect on GH release and IGF-I would increase SRIF mRNA representing a negative feedback mechanism regulating GH secretion. Preprosomatostatin (ppSRIF) mRNA levels within the periventricular nucleus (PeVN) were measured with in situ hybridization in ovariectomized female rat pups (n = 5 per group). Infusions were delivered sc via either a Silastic capsule (oil, 10 or 60 μg/ml estradiol) or an osmotic minipump (acetic acid, 120 or 240 μg IGF-I/day). Following ovariectomy on Day 21, animals were treated for either 1 or 7 days beginning on Day 24 of age. A total of 18 treatment groups were evaluated, including control, estradiol alone, IGF-I alone, and estradiol and IGF-I combined at both doses and treatment durations. Quantification of the area, density, and integrated density for ppSRIF mRNA within the PeVN revealed that treatments for only 1 day had no effect on the expression of ppSRIF mRNA, while those lasting 7 days significantly altered ppSRIF mRNA grain area and density. Both estradiol and IGF-I treatment at either dose significantly lowered ppSRIF mRNA and the decrease was exacerbated when estradiol and IGF-I were given in combination at either dose. Serum levels of rGH were not affected by any treatment. These data are consistent with the hypothesis that estradiol facilitates GH secretion during development, in part, by diminishing the inhibitory tone of SRIF via a decrease in ppSRIF mRNA. These data also suggest that any negative feedback action of peripheral increase in IGF-I on GH secretion is not mediated through regulation of SRIF mRNA in prepubertal rats.