afimoxifene and estrone-sulfate

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.

Topics: Animals; Cells, Cultured; Culture Media; DNA; Estradiol; Estrogen Antagonists; Estrone; Female; Guinea Pigs; Polyunsaturated Alkamides; Pregnancy; Tamoxifen; Uterus; Vagina

Endometrial guinea-pig glandular epithelial cells grown in primary culture incorporated [3H] thymidine. After three washings with a steroid-free medium, they were made quiescent and arrested in the G0/G1 phase. However, they remained hormone-responsive and resumed the cellular cycle after stimulation by 10(-6) M oestrone sulphate but not by oestradiol-17 beta.

Topics: Animals; Cell Differentiation; Cell Division; Cells, Cultured; DNA; Endometrium; Epithelial Cells; Estradiol; Estrone; Female; Guinea Pigs; Progesterone; Sulfotransferases; Sulfurtransferases; Tamoxifen

The comparative effect of oestradiol-17 beta, oestrone and oestrone-3-sulphate was examined on guinea-pig endometrium in primary culture. A parallel study was conducted in vivo to appreciate hormonal effects on the uterine luminal surface of ovariectomized guinea-pigs. Scanning electron microscopy studies showed that uterine epithelial cells were responsive to physiological concentrations of E2, E1 and E1S. Their plasma membrane was dramatically modified by 2.10(-9) M E2 and 10(-7) M E1S, but there are clear qualitative differences between the effect of E2 and of E1S. These effects were abolished by progesterone or 4-hydroxy-tamoxifen. Guinea-pig uterine epithelial cells in primary culture and in vivo are responsive to E2 and to E1S but their response to E1S appears to be more specific and can be distinguished by the cell surface morphology.

Topics: Animals; Endometrium; Epithelium; Estradiol; Estrogen Antagonists; Estrogens; Estrone; Female; Guinea Pigs; In Vitro Techniques; Microscopy, Electron, Scanning; Microvilli; Progesterone; Tamoxifen