Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats.
Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid.
D000818:Animals; D002250:Carbon Radioisotopes; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000378:metabolism*; D004997:Ethinyl Estradiol; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats
D002250:Carbon Radioisotopes; D003840:Deoxycholic Acid; D004997:Ethinyl Estradiol