Direct effect of ethanol on adrenocorticotropin (ACTH) release in vitro

In order to determine whether the pituitary directly contributes to the stimulatory action of ethanol on adrenocorticotropin (ACTH) release, the response of rat pituitaries to ethanol was studied in vitro. Acute exposure of superfused rat pituitaries to ethanol (20-200 mg/dl) produced dose-related increases in ACTH which were significant at doses of 40, 80 and 160 mg/dl. The response to each dose was multiphasic, consisting of three peaks of ACTH in the 28-min sampling period after addition of ethanol. The dose-response profile of each peak revealed a maximally effective stimulatory dose of 40 mg/dl of ethanol and the direct stimulatory effect decreased with higher doses, resulting in a bell-shaped pattern. In contrast, ovine corticotropin-releasing factor, in doses of 1.0 to 10.0 nM, produced a single dose-dependent ACTH response, indicating a unitary mechanism for its action as opposed to the probable multiple mechanisms of ethanol's action on the corticotrophs. These results indicate that low doses of ethanol act directly on the pituitary to induce ACTH release, while higher doses may have their primary site of action on the hypothalamus.