Effects of Age and Sex on Rat Bile Acid Metabolism1

A study was made of the effects of age (1 through 450 days) and sex on bile acid half-lives, pool sizes, and spectra. No significant sex or age differences were found in the cholic or chenodeoxycholic pool half-lives. Chenodeoxycholic acid half-lives were considerably shorter than corresponding cholic acid half-lives in all groups (cholic acid ≅ 3.5 days; chenodeoxycholic acid ≅ 2.0 days). With respect to pool sizes, from 1 through 15 days the pools of females and males were equal in size and contained only cholic acid, possibly because the liver enzyme systems necessary for chenodeoxycholic acid synthesis had not yet developed. From 27 through 450 days, the pools of females contained major concentrations of both cholic and chenodeoxycholic acid. In contrast the male pools from 46 to 450 days contained only traces of chenodeoxycholic acid, along with cholic acid concentrations about equal to those of female rats. This lack of chenodeoxycholic acid in the male bile acid pool, which could result from the action of androgens or estrogens on the bile acid synthetic pathway, has implications with respect to the relative ability of mature male and female rats to handle body cholesterol. The secondary bile acids (a- and β-muricholic and deoxycholic acids) did not appear in the pools until day 46. From then through 450 days, the concentrations of these acids were similar for the two sexes although there were individual variations. The fact that a- and β-muricholic acids are present in the adult male pool, although chenodeoxycholic acid is absent, suggests the possibility that alternate pathways may exist for the synthesis of the muricholic acids which do not involve chenodeoxycholic acid.