Increased hypothalamic somatostatin mRNA following dexamethasone administration in rats

There is increasing evidence to suggest that supraphysiological doses of glucocorticoids suppress growth hormone secretion in vivo by augmenting somatostatin release from the hypothalamus; previously, we reported an increase in hypothalamic somatostatin content in dexamethasone-treated rats. To further examine whether the production of somatostatin really is augmented, hypothalamic somatostatin mRNA levels were determined by the Northern blot technique in female rats receiving 330 micrograms of dexamethasone daily for three days. In two series of experiments, hypothalamic somatostatin mRNA levels in dexamethasone-treated rats were significantly (p < 0.05) increased to 133 +/- 19 (mean +/- SD)% and 153 +/- 38% of the controls. In the dexamethasone-treated rats, plasma growth hormone levels were markedly suppressed compared with those of the controls. These results further support the hypothesis that pharmacological doses of glucocorticoids increase the production and release of somatostatin from the hypothalamus and thus inhibit growth hormone secretion, overriding the direct stimulatory effect of glucocorticoids on growth hormone production at the pituitary level.