COMPARISON OF THE EFFECTS OF ALCOHOL AND ACETALDEHYDE ON PROOPIOMELANOCORTIN MESSENGER-RNA LEVELS AND BETA-ENDORPHIN SECRETION FROM HYPOTHALAMIC NEURONS IN PRIMARY CULTURES

The effects of acute and chronic treatments with ethanol and acute tre atments with an ethanol metabolite, acetaldehyde, on proopiomelanocort in (POMC) mRNA expression were compared with those of these agents on the secretion of a POMC gene product, beta-endorphin (beta-EP) peptide . The level of POMC mRNA in cultured cells was determined using an RNa se protection assay, and the accumulation of immunoreactive beta-EP (I R-beta-EP) peptide in the culture medium was measured by radioimmunoas say. Treatment of hypothalamic cells with 25-, 50-, and 100-mM doses o f ethanol or 12.5 and 25 mu M acetaldehyde for 3 h increased POMC mRNA levels. The stimulatory effect of ethanol on POMC mRNA levels lasted for a period of 12 h, although the percentage increase of the ethanol- stimulated mRNA level was gradually reduced over time. Acute treatment s with ethanol and acetaldehyde also elevated IR-beta-EP secretion fro m the cultured neurons for a period of 12 h, and the IR-beta-EP secret ory response developed desensitization after 24 h of ethanol incubatio n. The close association between the ethanol-induced IR-beta-EP secret ion and ethanol-regulated POMC mRNA expression suggests that ethanol r egulates both secretion and production of beta-EP peptide in the hypot halamic neurons. (C) 1994 Academic Press, Inc.