Transformation of estrone, estradiol, and estrone sulfate in uterine and vaginal isolated cells of fetal guinea pig. Effect of various antiestrogens in the conversion of estrone sulfate to estradiol.

The metabolism of physiological concentrations (5 x 10(-9) M) of [3H]estrone (E1), [3H]estradiol (E2), and [3H]estrone sulfate (E1S) was studied in isolated fetal uterine and vaginal cells of guinea pigs in culture. After 24 hours of incubation in both cells, a large percentage (40-60%) of E1 is converted to E2; however, after incubation of E2, most of the radioactive material (45-65%) corresponds to unchanged E2. Similarly, in the incubation medium the concentration of E2 is significantly higher related to E1 after incubation with E1 or E2. An intense sulfotransferase activity is found for both estrogens, whereas in the culture medium the respective sulfates represent 27-45% of the total radioactive material after incubation with the uterine cells and 15-24% for the vaginal cells. Using E1S, significant hydrolysis is observed in both cells and the analysis of the freed radioactive material indicated a high percentage in E2 (66% in the uterine cells and 71% in the vaginal cells). The conversion of E1S to E2 was strongly decreased by the antiestrogens: tamoxifen, 4-hydroxy-tamoxifen, and ICI 164,384. The inhibitory effect in relation to the incubation with E1S only was 43-66% in the uterine cells and 50-85% in the vaginal cells. The present data suggest that estrogen sulfates can play an important biological role in the target tissues of the fetus, and that the enzymatic mechanisms of the bioavailability of E2 for the biological responses of the hormone can be operated in the target tissue itself.