THE EFFECTS OF MILD ETHANOL INTOXICATION ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN NONALCOHOLIC MEN

Historically, ethanol exposure has been thought to stimulate the hypot halamic-pituitary-adrenal (HPA) axis. However, recent studies have dem onstrated decreased responsiveness to metyrapone and insulin-induced h ypoglycemia in alcoholic subjects. The present study investigated in m ore detail the effect of acute ethanol ingestion (0.75 g/kg) on the HP A axis in healthy nonalcoholic men (n = 14). In study 1, plasma ACTH/c ortisol levels were determined basally and every 30 min over a 180-min period after the ingestion of placebo or ethanol (n = 8). When the su bjects were analyzed as a group, ethanol did not alter ACTH or cortiso l levels. However, in two of eight subjects, ethanol ingestion was acc ompanied by a rise in plasma ACTH. In study 2, ethanol or placebo was ingested over 15 min, and 1 mug/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 A CTH responses to oCRH were blunted during the ethanol session (peak AC TH, 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); A divided by baseline X 100, 131 +/- 28 vs. 197 +/- 29% (P = 0.041); are a 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 o r placebo was ingested over 15 min, and 0.25 mug ACTH-(1-24) was admin istered (n = 5). Cortisol levels, determined 20 min before and 0, 30, 60, and 90 min after ACTH treatment, were not altered by ethanol admin istration. In summary, mildly intoxicating doses of ethanol did not st imulate the HPA axis in six of eight subjects. However, mild intoxicat ion 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.