Influence of sex and sex steroids on bilirubin uridine diphosphate-glucuronosyltransferase activity of rat liver.

Bilirubin uridine diphosphate-glucuronosyltransferase activity was markedly higher in liver preparations of adult female rats when compared with adult male rats. Ovariectomy decreased the levels in females whereas orchiectomy produced an increase in males. Totally opposite results were obtained when assaying p-nitrophenol uridine diphosphate-glucuronosyl-transferase; this suggests the existence of different enzymes. Administration of physiologic amounts of testosterone decreased enzyme activities in orchiectomized males to normal levels. Estradiol had no effect but progesterone significantly enhanced the transferase activity of gonadectomized females. The effect was more pronounced when progesterone was associated with estradiol. The combined treatment of ovariectomized rats resulted in physiologic plasma levels of sex steroids and could increase the levels of glucuronosyl-transferase to values of normal females. Male and female sex hormones thus exert opposite effects on bilirubin uridine diphosphate-glucuronosyltransferase. If applicable to humans, this might explain the differences in serum bilirubin levels in adult men and women, and in the prevalence of Gilbert's syndrome.