Immunocytochemical and molecular analysis of the effects of glucocorticoid treatment on the hypothalamic-somatotropic axis in the rat.

Glucocorticoids are potent inhibitors of linear growth and growth hormone (GH) secretion when secreted or administered in pharmacological amounts in vivo. The mechanisms involved require further clarification although enhanced somatostatin tone has been suggested to play a role. In this study, we investigated the effects of excess glucocorticoids on pituitary GH, hypothalamic GHRH and hypothalamic somatostatin through immunocytochemical (ICC) and mRNA analysis. Twelve adult male rats were injected daily with dexamethasone (40 micrograms/day, i.p.) or saline for 4 days. ICC studies were performed on brain sections from the rostral, middle and caudal regions of the median eminence of the hypothalamus using the avidin-biotin-peroxidase method. Messenger RNA analyses were performed using sense and antisense riboprobes produced from GH, GHRH and somatostatin cDNAs. Immunocytochemical results were generated for the percent area and intensity (optical density) of immunostaining in the median eminence. Glucocorticoids increased somatostatin immunostaining of the rostral, middle and caudal regions of the median eminence while GHRH staining was only reduced in the rostral region of the median eminence and unchanged in the other hypothalamic regions. GH and somatostatin mRNA levels dramatically increased following glucocorticoid treatment concomitantly with a decrease in GHRH mRNA levels. Our data suggest that increased somatostatin synthesis and storage and a decrease in GHRH mRNA synthesis play a major role in the GH inhibitory effects of glucocorticoids.