Effect of Various Steroids on the Hepatic Glucuronidation and Biliary Excretion of Bilirubin

Abstract

In rats, treatment with spironolactone or pregnenolone-16α-carbonitrile (PCN) accelerates bile flow and enhances hepatic microsomal bilirubin–UDP glucuronyltransferase activity (EC 2.4.1.17) and the biliary transport maximum (Tm) of bilirubin. The distribution of ethylanthranilate azo-pigments in fractions separated by thin-layer chromatography also indicates increased glucuronidation of bilirubin. These findings explain the mechanism of enhanced serum bilirubin disappearance in rats treated with the steroids.

Effect of Pregnenolone-16α-Carbonitrile on Bilirubin- and Sulfobromophthalein-Binding to Hepatic Y and Z Proteins in the Rat

“…In addition, PCN induces Z protein and, as an associated change, it increases the capacity of the liver to take up and store bilirubin and BSP. These findings are in total agreement with earlier investigations (17,18) in which it was shown that PCN enhances serum bilirubin clearance in rats.…”

“…Like phénobarbital, certain microsomal enzyme inducers -for instance, pregnenolone16a-carbonitrile (PCN) and spironolactonehave been shown to accelerate the clearance of bilirubin from serum (17), stimulate bile flow and increase hepatic microsomal bilirubin-UDP glucuronyltransferase activity as well as die biliary Tm of bilirubin (2,18).…”

“…The induction by PCN of Y protein -the major organic anion binding protein in the liver (6) -suggests a possible effect of this cyanosteroid on tissue bilirubin distribution, an effect wliich may be independent of its direct influence on the microsomal enzyme system. In view of its stimulation of bilirubin glucuronyltransferase and lowering of plasma bilirubin levels in ex perimental hyperbilirubinemia (18), PCN -like phénobarbital -appears to fulfill most of the requirements as an aid in the prevention and/or treatment of kemicterus.…”

Conjugation and Maximal Biliary Excretion of Bilirubin in the Rat During Pregnancy and Lactation and During Estroprogestogen Treatment

“…Different steroids might be involved or other hormones might be required to allow an effect of estrogens and progestogens to become manifest, thus exerting a permissing effect. It has also been proposed that alterations of drug-metabolizing enzymes during pregnancy is a consequence of a shift of hepatic progesterone metabolism from the hydroxylation pathway, producing inducers of microsomal enzymes such as pregnenolone 16a-carbonitrile, to the reduction pathway, producing inhibitors of microsomal enzymes such as pregnanediol (29). This hypothesis could also explain the present results, since pregnenolone-16a-carbonitrile was found to induce hepatic bilirubin conjugation (29) while pregnanendiol was found to inhibit it (30).…”

Effect of pregnenolone‐16 alpha‐carbonitrile (PCN) on bilirubin clearance in man.

“…In the rat, PCN increases bile flow as well as the glucuronidation of bilirubin and clearance of sulphobromophthelein (BSP) (Zsigmond & Solymoss, 1972;Solymoss & Zsigmond, 1973). It also counters toxic effects of many substances in the rat (Selye, 1971).…”