THE EFFECTS OF AN ANTIPROGESTIN, MIFEPRISTONE, AND AN ANTIESTROGEN, TAMOXIFEN, ON ENDOMETRIAL 17-BETA-HYDROXYSTEROID DEHYDROGENASE AND PROGESTIN AND ESTROGEN-RECEPTORS DURING THE LUTEAL-PHASE OF THE MENSTRUAL-CYCLE - AN IMMUNOHISTOCHEMICAL STUDY

The effects of a progesterone antagonist, mifepristone (RU486), and an estrogen antagonist, tamoxifen, given during the early luteal phase o n endometrial 17beta-hydroxysteroid dehydrogenase (17HSD) and estrogen (ER) and progesterone (PR) receptors were studied. Eleven regularly m enstruating women were studied during control and treatment cycles. In the treatment cycle on day LH+2 (2 days after the peak serum LH conce ntration), 10 subjects received a single dose of 200 mg mifepristone, and 9 received 2 doses of 40 mg tamoxifen on days LH+2 and LH+3. In ad dition, 4 subjects received 400 mg mifepristone in a separate treatmen t cycle. 17HSD, ER, and PR were measured immunohistochemically in endo metrial tissue specimens taken on days LH+6 to LH+8. Blood samples wer e conducted during control and treatment cycles, and serum estradiol, progesterone, and LH concentrations were quantified by RIA. Administra tion of mifepristone blocked the induction of 17HSD by progesterone an d prevented the expression of 17HSD in gland and surface epithelial ce lls in 8 patients. In 2 patients, staining of 17HSD was seen during bo th the control and mifepristone treatment cycles. The higher dose of m ifepristone additionally given to four subjects did not block the expr ession of 17HSD in 2 cases where blocking was observed with the lower dose of mifepristone, and in 1 of these patients, very strong staining of 17HSD was observed in basal cells beneath the epithelial cells. ER and PR showed intense staining in the nuclei of both gland and stroma l cells in mifepristone treatment cycles, whereas receptor staining wa s faint or absent in the respective control cycles. Tamoxifen did not have any significant effect on staining of 17HSD or the abundance of r eceptors. Serum concentrations of estradiol, progesterone, and LH were not significantly affected by the administration of mifepristone or t amoxifen. This study reveals that mifepristone, administered in the ea rly luteal phase, usually blocks the expression of 17HSD and the down- regulation of PR and ER. However, the expression of 17HSD in some pati ents may reflect the ineffectiveness of the mifepristone treatment use d to prevent implantation in certain subjects.