Comparison of the effects of alcohol and acetaldehyde on proopiomelanocortin mRNA levels and beta-endorphin secretion from hypothalamic neurons in primary cultures.

The effects of acute and chronic treatments with ethanol and acute treatments with an ethanol metabolite, acetaldehyde, on proopiomelanocortin (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 RNase protection assay, and the accumulation of immunoreactive beta-EP (IR-beta-EP) peptide in the culture medium was measured by radioimmunoassay. Treatment of hypothalamic cells with 25-, 50-, and 100-mM doses of ethanol or 12.5 and 25 microM 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 treatments with ethanol and acetaldehyde also elevated IR-beta-EP secretion from the cultured neurons for a period of 12 h, and the IR-beta-EP secretory response developed desensitization after 24 h of ethanol incubation. The close association between the ethanol-induced IR-beta-EP secretion and ethanol-regulated POMC mRNA expression suggests that ethanol regulates both secretion and production of beta-EP peptide in the hypothalamic neurons.