Glucocorticoid effect on the level of corticotropin messenger RNA activity in rat pituitary.

In an attempt to understand the molecular mechanism underlying the depressive effect of glucocorticoids on corticotropin production, the level of corticotropin messenger RNA activity in rat pituitaries was measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The large translation product of corticotropin messenger RNA was identified and quantitated by indirect immunoprecipitation with antibody against corticotropin. The level of corticotropin messenger RNA activity was increased 3- to 6-fold by adrenalectomy. Dexamethasone administration to adrenalectomized rats resulted in a marked suppression of corticotropin messenger RNA activity. Cortisol and corticosterone also exhibited a suppressive effect but were less effective than dexamethasone. In contrast, nonglucocorticoids such as progesterone and aldosterone had no suppressive effect. These results indicate that at least part of the glucocorticoid effect on corticotropin production in the pituitary is exerted at the pretranslational level.