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 horm one (GH) secretion when secreted or administered in pharmacological am ounts in vivo. The mechanisms involved require further clarification a lthough enhanced somatostatin tone has been suggested to play a role, In this study, we investigated the effects of excess glucocorticoids o n pituitary GH, hypothalamic GHRH and hypothalamic somatostatin throug h immunocytochemical (ICC) and mRNA analysis. Twelve adult male rats w ere injected daily with dexamethasone (40 mu g/day, i.p.) or saline fo r 4 days. ICC studies were performed on brain sections from the rostra l, middle and caudal regions of the median eminence of the hypothalamu s using the avidin-biotin-peroxidase method. Messenger RNA analyses we re performed using sense and antisense riboprobes produced from GH, GH RH and somatostatin cDNAs. Immunocytochemical results were generated f or the percent area and intensity (optical density) of immunostaining in the median eminence. Glucocorticoids increased somatostatin immunos taining of the rostral, middle and caudal regions of the median eminen ce while GHRH staining was only reduced in the rostral region of the m edian eminence and unchanged in the other hypothalamic regions. GH and somatostatin mRNA levels dramatically increased following glucocortic oid treatment concomitantly with a decrease in GHRH mRNA levels. Our d ata suggest that increased somatostatin synthesis and storage and a de crease in GHRH mRNA synthesis play a major role in the GH inhibitory e ffects of glucocorticoids.