Characterization of an early inhibitory effect of glucocorticoids on stimulated adrenocorticotropin and endorphin release from a clonal strain of mouse pituitary cells.

Abstract

The ability of glucocorticoid steroid hormones to inhibit release of ACTH and endorphin has been studied in the mouse pituitary tumor cell strain, AtT-20/ D l6v. Inhibition of release of both peptides was first detectable at 30 min (to 80–90% of control release) and was maximal (30–50% of control) by 3–4 h of pretreatment with dexamethasone (1 × 10-6 M). Glucocorticoids did not consistently affect basal hormone release, but they inhibited release stimulated 4-to 8-fold by hypothalamic extract, phorbol esters, or 8-Br-cAMP but not high K+-stimulated release. The inhibitory effect was glucocorticoid specific and dose dependent with ED50S for dexamethasone, corticosterone, and cortisol close to their reported KdS for binding to the cytoplasmic glucocorticoid receptor. Inhibition of release was blocked by cycloheximide (1 × 10-5 M), suggesting that protein synthesis was required. Experiments were performed to determine the site of action of glucocorticoids. Steroid pretreatment for up to 6 h had no effect on ...