Beta-endorphin genetics in the etiology of alcoholism.
"Reinforcing" effects are ascribed to endogenous opioids, particularly to the pro-opiomelanocortin (POMC)-derived beta-endorphin 1-31, the most potent opiate-active substance. Alcohol induces variations in the genetic processing of the precursor POMC and of beta-endorphin at different levels. Studies focused on changes in POMC gene expression (mRNA quantitation) and post-translational processing. Chronic alcohol intake significantly reduces POMC mRNA in the lobes of the pituitary. In inbred strains of mice, genotypic differences are seen in post-translational processing of hypothalamic beta-endorphin, thus inducing differences in alcohol sensitivity. Clinical studies show a disproportion of POMC cleavage products in the CSF of chronic alcoholics (reduced beta-endorphin versus increased ACTH contents), together with remarkable indications for baseline differences in beta-endorphin levels. Errors within the genetic sequence of POMC are suggested to underlie alcohol-seeking behavior.
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D000437:Alcoholism / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D001615:beta-Endorphin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D012333:RNA, Messenger; D000431:Ethanol; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin