title: Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Germany. hinz@pharmakologie.uni-erlangen.de
authors.forename: B
authors.initials: B
authors.lastname: Hinz
authors.forename: R
authors.initials: R
authors.lastname: Hirschelmann
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D005246:Feedback / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000819:agonists / Q000037:antagonists & inhibitors; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D000732:Androstanols; D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D011987:Receptors, Steroid; D003609:Dactinomycin; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone