Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver.

Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate.