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

Abstract

The metabolism of physiological concentration (5 × 10 −9 M) of [ 3H]estrone (E 1), [ 3H]estradiol (E 2), and [ 3H]estrone sulfate (E 1S) 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 E 1 is converted to E 2; however, after incubation of E 2, most of the radioactive material (45–65%) corresponds to unchanged E 2. Similarly, in the incubation medium the concentration of E 2 is significantly higher related to E 1 after incubation with E 1 or E 2. 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 E 1S, significant hydrolysis is observed in both cells and the analysis of the freed radioactive material indicated a high percentage in E 2 (66% in the uterine cells and 71% in the vaginal cells). The conversion of E 1S to E 2 was strongly decreased by the antiestrogens: tamoxifen, 4-hydroxy-tamoxifen, and ICI 164,384. The inhibitory effect in relation to the incubation with E 1S 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 E 2 for the biological responses of the hormone can be operated in the target tissue itself.