Gender-related differences in mouse hepatic ethanol metabolism.

The effect of an acute oral load of 2 g ethanol/kg body weight was studied in a group of male and female 10-wk-old C3H/HeNCrj (C3H/He) mice to investigate gender change throughout differences of the hepatic ethanol metabolism of mice. The following parameters were measured in the serum from 0 h to 3 h after the start of the experiment: ethanol, acetaldehyde, and acetate. Their concentrations in the serum in female mice tended to show lower levels than in male mice. In female mice, the concentration of ethanol at 1 h and the concentration of acetate at 1 h, 2 h, and 3 h after ethanol administration showed significantly lower levels than in male mice. Ten-week-old male and female C3H/He mice were subcutaneously injected 50 microg/kg body weight beta-estradiol and 1.45 mmol/kg body weight testosterone propionate (testosterone) in olive oil, respectively, and changes in the activity of enzymes related to the hepatic ethanol metabolism of mice were examined at 24 h after the administration of sex hormones. The activity of the cytosolic alcohol dehydrogenase (ADH) and microsomal aniline hydroxylase (ANH) and the low Km, high Km and total aldehyde dehydrogenase (AlDH) activities in the mitochondrial, the cytosolic, and the microsomal fraction of the liver were higher. Moreover, the density of the band of CYP2E1 in the microsome in female mice was stronger than in male mice, and in the microsomal fraction of the liver, the total content of cytochrome P-450 (CYP) and ethoxyresorufin O-dealkylase (EROD) activity in male mice showed significantly higher values than in female mice. The density of the band of CYP2E1 and the three activities of AlDH in the hepatic mitochondrial fraction of male mice increased significantly under treatment with beta-estradiol. The three activities of AlDH of the cytosolic fraction of the liver in female mice significantly decreased under treatment with testosterone. The present findings suggested that in C3H/He mice livers, the rate of ethanol metabolism is faster in females than in males, and the enzymes related to ethanol metabolism are controlled by testosterone or beta-estradiol. It is suggested that ethanol and its metabolite disappear faster from the serum of female mice than from the serum of male mice because the activities of hepatic enzymes related to ethanol metabolism are higher in female mice than in male mice. C3H/He mice, hepatic ethanol metabolism, gender different, ADH, AlDH