Induction of Pituitary Sensitivity to Interleukin-1: A New Function for Corticotropin-Releasing Hormone

• Published in: Biochemical and biophysical research communications Vol. 198; no. 2; pp. 480 - 484
• Main Authors: Payne, L.C., Weigent, D.A., Blalock, J.E.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 28.01.1994; Elsevier
• Subjects: Adrenocorticotropic Hormone - metabolism; Animals; Biological and medical sciences; Corticotropin-Releasing Hormone - antagonists & inhibitors; Corticotropin-Releasing Hormone - pharmacology; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Interleukin-1 - pharmacology; Male; Peptide Fragments - pharmacology; Pituitary Gland - drug effects; Rats; Rats, Sprague-Dawley; Vertebrates: endocrinology; Immune response; Rat; Hypothalamohypophysoadrenal axis; Cytokine; Peptide hormone; Rodentia; ACTH-RH; ACTH; Stress; Signal transduction; Vertebrata; Mammalia; Interleukin 1; Hormone releasing factor; Release
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.1070

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-imediated-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, α-helical (αh) 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.