The effects of mild ethanol intoxication on the hypothalamic-pituitary-adrenal axis in nonalcoholic men

Historically, ethanol exposure has been thought to stimulate the hypothalamic-pituitary-adrenal (HPA) axis. However, recent studies have demonstrated decreased responsiveness to metyrapone and insulin-induced hypoglycemia in alcoholic subjects. The present study investigated in more detail the effect of acute ethanol ingestion (0.75 g/kg) on the HPA axis in healthy nonalcoholic men (n = 14). In study 1, plasma ACTH/cortisol levels were determined basally and every 30 min over a 180-min period after the ingestion of placebo or ethanol (n = 8). When the subjects were analyzed as a group, ethanol did not alter ACTH or cortisol levels. However, in two of eight subjects, ethanol ingestion was accompanied by a rise in plasma ACTH. In study 2, ethanol or placebo was ingested over 15 min, and 1 microgram/kg ovine (o) CRH was administered (n = 9). Hormone levels were determined at 20 min before and 0, 15, 30, 60, and 90 min after iv oCRH. Compared to responses to placebo, plasma ACTH responses to oCRH were blunted during the ethanol session [peak ACTH, 14.2 +/- 1.4 vs. 20.3 +/- 3.1 pmol/L (P = 0.036); peak value minus baseline (delta), 7.3 +/- 1.4 vs. 13.4 +/- 2.6 pmol/L (P = 0.017); delta divided by baseline x 100, 131 +/- 28 vs. 197 +/- 29% (P = 0.041); area under the ACTH curve, 1082 +/- 116 vs. 1529 +/- 232 pmol/min.L (P = 0.024)]. Ethanol ingestion also significantly blunted plasma cortisol levels after oCRH compared to placebo treatment. In study 3, ethanol or placebo was ingested over 15 min, and 0.25 microgram ACTH-(1-24) was administered (n = 5). Cortisol levels, determined 20 min before and 0, 30, 60, and 90 min after ACTH treatment, were not altered by ethanol administration. In summary, mildly intoxicating doses of ethanol did not stimulate the HPA axis in six of eight subjects. However, mild intoxication significantly impaired oCRH-stimulated ACTH/cortisol secretion. We speculate that mild intoxication with ethanol may impair the ability of the HPA axis to respond to physiological stressors.