Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats

Jensen, R.T.; Davis, R.A.; Kern, F.

Gastroenterology 73(2): 314-320

1977


ISSN/ISBN: 0016-5085
PMID: 873132
Accession: 005665449

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Abstract
Deoxycholic acid conjugation, transport capacity and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats had a lower capacity to transport deoxycholic aicd 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 7.alpha.-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 < 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. 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.