B Hinz1, R Hirschelmann. 1. Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Germany. hinz@pharmakologie.uni-erlangen.de
Abstract
PURPOSE: The present study investigates fast negative feedback actions of corticosterone (corticosteroid type I/type II receptor agonist) and RU 28362 (corticosteroid type II receptor agonist) on corticotropin-releasing factor (CRF)-induced adrenocorticotropic hormone (ACTH) secretion in rats. METHODS: To induce fast feedback, glucocorticoids were administered intravenously immediately before injection of the hypophyseotropic stimulus CRF. Plasma ACTH levels, being determined 5 to 30 min thereafter, were used as markers of fast feedback. RESULTS: Fast inhibitory effects on CRF-induced ACTH secretion became evident within 15 min (corticosterone) and 5 min (RU 28362) after steroid administration. Rapid feedback inhibition was also observed in the presence of other corticosteroids (cortisol, dexamethasone, aldosterone), whereas structurally-unrelated steroids (beta-estradiol, progesterone, potassium canrenoate, alphaxalone) were inactive in this respect. Pretreatment of rats with the corticosteroid type II receptor antagonist RU 486 or the transcription inhibitor actinomycin D left fast feedback effects unaltered. CONCLUSIONS: Our results demonstrate that glucocorticoids exert fast negative feedback at the pituitary level via a mechanism that is independent of corticosteroid type II receptor occupation and de novo synthesis of mRNA. In conclusion, corticosteroid-specific nongenomic effects may underly rapid glucocorticoid responses on CRF-induced ACTH secretion.
PURPOSE: The present study investigates fast negative feedback actions of corticosterone (corticosteroid type I/type II receptor agonist) and RU 28362 (corticosteroid type II receptor agonist) on corticotropin-releasing factor (CRF)-induced adrenocorticotropic hormone (ACTH) secretion in rats. METHODS: To induce fast feedback, glucocorticoids were administered intravenously immediately before injection of the hypophyseotropic stimulus CRF. Plasma ACTH levels, being determined 5 to 30 min thereafter, were used as markers of fast feedback. RESULTS: Fast inhibitory effects on CRF-induced ACTH secretion became evident within 15 min (corticosterone) and 5 min (RU 28362) after steroid administration. Rapid feedback inhibition was also observed in the presence of other corticosteroids (cortisol, dexamethasone, aldosterone), whereas structurally-unrelated steroids (beta-estradiol, progesterone, potassium canrenoate, alphaxalone) were inactive in this respect. Pretreatment of rats with the corticosteroid type II receptor antagonist RU 486 or the transcription inhibitor actinomycin D left fast feedback effects unaltered. CONCLUSIONS: Our results demonstrate that glucocorticoids exert fast negative feedback at the pituitary level via a mechanism that is independent of corticosteroid type II receptor occupation and de novo synthesis of mRNA. In conclusion, corticosteroid-specific nongenomic effects may underly rapid glucocorticoid responses on CRF-induced ACTH secretion.
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