title: Induction of pituitary sensitivity to interleukin-1: a new function for corticotropin-releasing hormone.
abstract: Activation of the hypothalamic-pituitary-adrenal axis to release corticotropin-releasing hormone (CRH), corticotropin (ACTH), and glucocorticoids during inflammatory stress is now considered a key function of interleukin-1 (IL-1). Current dogma suggests that in vivo ACTH release due to IL-1 is indirect and entirely results from IL-1-mediated-CRH release from the hypothalamus. The present findings show that low levels of exogenous or endogenous CRH can sensitize the pituitary gland to the direct ACTH releasing activity of IL-1. Once sensitized, IL-1 induced ACTH release is not inhibitable by the CRH antagonist, alpha-helical (alpha h) CRF [9-41]. Thus, IL-1 effects ACTH release at the level of both the hypothalamus and pituitary gland. Perhaps more importantly, the results suggest pituitary sensitization to cytokines, such as IL-1, as a new function for CRH. This action would represent a novel interactive point between the nervous, endocrine, and immune systems whereby very mild psychological or physical stress could have a profound impact on an inflammatory response by increasing pituitary sensitivity to immunological mediators such as IL-1.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham 35294-0005.
authors.forename: L C
authors.initials: LC
authors.lastname: Payne
authors.forename: D A
authors.initials: DA
authors.lastname: Weigent
authors.forename: J E
authors.initials: JE
authors.lastname: Blalock
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007375:Interleukin-1; D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)