Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats

Purpose. The present study investigates fast negative feedback actions of c orticosterone (corticosteroid type I/type II receptor agonist) and RU 28362 (corticosteroid type II receptor agonist) on corticotropin-releasing facto r (CRF)-induced adrenocorticotropic hormone (ACTH) secretion in rats. Methods. To induce fast feedback, glucocorticoids were administered intrave nously immediately before injection of the hypophyseotropic stimulus CRF. P lasma ACTH levels, being determined 5 to 30 min thereafter, were used as ma rkers of fast feedback. Results. Fast inhibitory effects on CRF-induced ACTH secretion became evide nt within 15 min (corticosterone) and 5 min (RU 28362) after steroid admini stration. Rapid feedback inhibition was also observed in the presence of ot her corticosteroids (cortisol, dexamethasone, aldosterone), whereas structu rally-unrelated steroids (beta -estradiol, progesterone, potassium canrenoa te, alphaxalone) were inactive in this respect. Pretreatment of rats with t he corticosteroid type II receptor antagonist RU 486 or the transcription i nhibitor actinomycin D left fast feedback effects unaltered. Conclusions. Our results demonstrate that glucocorticoids exert fast negati ve feedback at the pituitary level via a mechanism that is independent of c orticosteroid type II receptor occupation and de novo synthesis of mRNA. In conclusion, corticosteroid-specific non-genomic effects may underly rapid glucocorticoid responses on CRF-induced ACTH secretion.