Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli.
This review discusses some of the mechanisms through which alcohol (EtOH) alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis. In adult rats, acute EtOH treatment increases plasma ACTH and corticosteroids levels primarily by stimulating the release of corticotropin-releasing factor (CRF) and possibly vasopressin (VP) from nerve terminals in the median eminence. Increased CRF gene transcription in the hypothalamus may also be important. The HPA axis remains activated during chronic EtOH exposure, although habituation may take place. Changes in the responsiveness of hypothalamic neurons, a phenomenon itself dependent in part on a number of intermediate secretagogues, as well as decreased pituitary responsiveness to VP, all play a role. Finally, the activity of the HPA axis is influenced by exposure to EtOH during embryonic development, with mature offspring showing hyporesponsiveness to many stimuli. These altered responses appear to be caused in part by changes in the synthesis/release CRF, possibly under the influence of nitric oxide. CRF, VP, ACTH, and corticosteroids are important regulators of the immune system, behavior, metabolic pathways, and reproductive parameters. Alcohol therefore may influence such functions through the pathological secretion of these hormones. A better understanding of the mechanisms through which the drug alters their release thus may permit the development of therapies designed to alleviate some of the consequences of alcoholism.
Rivier
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Clayton foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037, USA.
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity; D013268:Stimulation, Chemical; D014667:Vasopressins / Q000097:blood
D014667:Vasopressins; D000431:Ethanol; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone