The Enterohepatic Circulation of Aldosterone Metabolites and its Sex-Dependence in Rats

Sephadex LH-20 and DEAP-LH-20 column chromatography demonstrated significant differences in the types of conjugates of aldosterone and its metabolites present in the bile of male and female rats. The bile of male rats contained mainly “glucuronides” and “monosulfates” of aldosterone and its metabolites, whereas the bile of female rats contained mainly “monosulfates” and “disulfates” of aldosterone and its metabolites. This difference appears to account for both the differences in the biliary excretion and the enterohepatic circulation of the radiometabolites of [3H]aldosterone in male and female rats. The enterohepatic circulation of aldosterone metabolites was demonstrated to be sizeable and sexdependent in intact rats. Following intraduodenal injection of male and female bile, containing radiometabolites of [3H]aldosterone, into rats of the same sex, a greater percentage of the injected radiometabolities appeared in both the bile and urine of the males than in the females. By 4 h, ca. 20% of the injected dose was excreted in the bile of males compared with ca. 9% in the females. During this 4 h time period, 5.5% of the injected radiometabolites was excreted in the urine of the males compared with less than 1% in the females. Intraduodenal injection of the fractions of the biliary metabolities and conjugates of aldosterone, separated by Sephadex LH-20, demonstrated that the “free metabolite and glucuronide” fraction was reabsorbed from the intestine into the enterohepatic circulation to a greater extent than the “mono- and di-sulfate” fractions. These findings suggest that the sex differences in the hepatic synthesis of the metabolities and conjugates of aldosterone account for the differences in the extent of the enterohepatic circulation of the biliary radiometabolities of [3H]aldosterone in male and female rats.