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 on endometrial 17 beta-hydroxysteroid dehydrogenase (17HSD) and estrogen (ER) and progesterone (PR) receptors were studied. Eleven regularly menstruating women were studied during control and treatment cycles. In the treatment cycle on day LH + 2 (2 days after the peak serum LH concentration), 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 addition, 4 subjects received 400 mg mifepristone in a separate treatment cycle. 17HSD, ER, and PR were measured immunohistochemically in endometrial tissue specimens taken on days LH + 6 to LH + 8. Blood samples were conducted during control and treatment cycles, and serum estradiol, progesterone, and LH concentrations were quantified by RIA. Administration of mifepristone blocked the induction of 17HSD by progesterone and prevented the expression of 17HSD in gland and surface epithelial cells in 8 patients. In 2 patients, staining of 17HSD was seen during both the control and mifepristone treatment cycles. The higher dose of mifepristone additionally given to four subjects did not block the expression 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 stromal cells in mifepristone treatment cycles, whereas receptor staining was faint or absent in the respective control cycles. Tamoxifen did not have any significant effect on staining of 17HSD or the abundance of receptors. Serum concentrations of estradiol, progesterone, and LH were not significantly affected by the administration of mifepristone or tamoxifen. This study reveals that mifepristone, administered in the early luteal phase, usually blocks the expression of 17HSD and the down-regulation of PR and ER. However, the expression of 17HSD in some patients may reflect the ineffectiveness of the mifepristone treatment used to prevent implantation in certain subjects.
Mäentausta
O
O
Biocenter, University of Oulu, Finland.
Svalander
P
P
Danielsson
K G
KG
Bygdeman
M
M
Vihko
R
R
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D000328:Adult; D015536:Down-Regulation; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008183:Luteal Phase / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology*; D011863:Radioimmunoassay; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis*; D013629:Tamoxifen / Q000494:pharmacology*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D013629:Tamoxifen; D015735:Mifepristone; D015067:17-Hydroxysteroid Dehydrogenases