The effect of growth hormone on the activity of alcohol dehydrogenase was determined in hepatocyte culture from normal and hypophysectomized male rats. Alcohol dehydrogenase activity was highest in hepatocytes harvested from hypophysectomized rats. The enzyme activity remained stable in hepatocytes harvested from normal rats during 2 to 6 days of culture but declined steadily in hepatocytes cultured from hypophysectomized rats. The combination of growth hormone (1 pg per ml) and corticosterone (1 p M ) increased alcohol dehydrogenase activity in hepatocytes from normal rats, while neither hormone alone had an effect. Corticosterone (1 p M ) prevented the decline of the enzyme activity in hepatocytes from hypophysectomized rats, and the combination of growth hormone (1 pg per ml) and corticosterone (1 p M ' ) resulted in a further increase in enzyme activity. The increases in alcohol dehydrogenase, due to the exposure of the hepatocytes to the combination of growth hormone and corticosterone, were associated with increases in the rate of ethanol elimination. These observations indicate that growth hormone enhances liver alcohol dehydrogenase activity and ethanol elimination, and that this effect is dependent on the permissive influence of corticosterone.
Liver alcohol dehydrogenase is the primary enzyme regulating rates of ethanol metabolism. The administration of growth hormone increases liver alcohol dehydrogenase activity in normal male rats (1). Increases in alcohol dehydrogenase activity in experimentally induced uremia ( 2 ) and after immobilization stress (3) are associated with increases in plasma growth hormone levels (1). However, alcohol dehydrogenase activity was also increased after hypophysectomy, and this increase was suppressed by the administration of growth hormone (1). These findings suggest that the action of growth hormone on the enzyme is modified by pituitary factors. Recent reports show that lesions of the periventricular nucleus and hypothalamus in male rats increase liver alcohol dehydrogenase activity (4). These lesions are known to reduce somatostatin content in the median eminence (5), thus resulting in increased growth hormone secretion. The complex hormone interactions that