Metabolism of [ 3H] 17β-dihydroequilin and [ 3H] 17β-dihydroequilin sulfate in normal postmenopausal women

Abstract

The metabolism of 17β-dihydroequilin and 17β-dihydroequilin sulfate was investigated after intravenous administration of [ 3H] 17β-dihydroequilin and [ 3H] 17β-dihydroequilin sulfate to postmenopausal women Urine was collected for 3 days and 46.2±10.5% and 54.5±8.7% of the injected dose of [ 3H] 17β-dihydroequilin and [17β- 3H]dihydroequilin sulfate was excreted in the urine respectively. The estrogens present in urine were extracted and fractionated into unconjugated, sulfate, and glucuronide conjugated forms. With both precursors, the major amount (63–64%) of metabolites were excreted in the urine conjugated with glucuronic acid. From the unconjugated, sulfate, and glucuronide fraction, 17β-dihydroequilenin, 17β-dihydroequilin, equilenin, and equilin were isolated. The conversions with both precursors were similar and 17β-dihydroequilenin was the major metabolite isolated from all three fractions; however, the highest levels of all four metabolites were present in the glucuronide fraction. Along with these identifiable metabolites, a large amount (51–81%) of radioactivity was present in the form of metabolites which are more polar than any of the known ring-B unsaturated estrogens. These appear to by polyhydroxy 17β-reduced ring-B unsaturated estrogens which remain to be identified. The in-vivo formation of equilenin and 17β-dihydroequilenin indicates the presence of the enzyme 6,8(9) steroid dehydrogenase in humans. (Steroids 59:389–394, 1994)