dihydrotestosterone-glucuronide and estriol-glucuronide

The cholestasis induced by estrogen metabolites has been postulated to be due to an inhibition of bile acid transport. Therefore, the uptake of [3H]taurocholate (TC) into isolated hepatocytes was examined in the presence of known cholestatic steroid glucuronides. The cholestatic D-ring glucuronide conjugates of estradiol, estriol, ethynylestradiol and dihydrotestosterone did not inhibit the uptake of TC suggesting that these organic anions are transported by different carrier systems. Estrone sulfate inhibited TC uptake 65% but did not decrease bile flow following i.v. administration to the rat (22 mumol/kg), under conditions which the steroid glucuronide estradiol-17 beta-(beta-D-glucuronide) ( E217G ) decreased bile flow 100%. The hepatocytic uptake of [3H] E217G (100 microM) was inhibited by estriol-16 alpha-(beta-D-glucuronide) (200 microM, 40%) and estradiol-17 beta-3-(beta-D-glucuronide) (200 microM, 22%) as well as by the organic anions bromosulfophthalein (150 microM, 57%), dibromosulfophthalein (150 microM, 59%), indocyanine green (150 microM, 62%), rose bengal (150 microM, 56%) and bilirubin (50 microM, 40%). Thus, the bile acids and steroid glucuronides are transported into the hepatocyte by different carrier systems so that the cholestasis induced by the steroid D-ring glucuronides cannot be explained by an inhibition of bile acid uptake. Furthermore, the hepatocytic uptake of E217G occurs by a carrier system similar to that for the other steroid glucuronides and organic anions.

Topics: Animals; Cholestasis; Dihydrotestosterone; Estradiol; Estriol; Estrogens; Ethinyl Estradiol; Female; In Vitro Techniques; Liver; Rats; Rats, Inbred Strains; Taurocholic Acid