Effect of U11, 100A and U11, 555A on plasma hormones and uterine mitoses in early pregnancy in the rat

Mature female rats were treated orally with U11, 100A and U11,555A on Day 2 of pregnancy and plasma levels of oestradiol-17β and progesterone were determined. Also examined were the mitotic patterns in the stromal, luminal epithelial and glandular cells of the uterus. Both compounds, at doses completely inhibiting implantation, eliminated the plasma oestradiol peak normally occurring about 22.00 hrs on Day 3 and also totally suppressed stromal mitoses but had little effect on epithelial and glandular mitoses. Lower doses of U11,555A permitting approximately 40% implantation did not lower the oestradiol peak but reduced stromal mitoses. A similar physiologically active dose of U11, 100A eliminated the oestradiol peak but did not completely suppress stromal mitoses. Progesterone levels in animals treated with these lower doses did not rise after Day 9 of pregnancy. Synthesis of oestradiol-17β in vitro from testosterone by ovaries of treated animals was significantly decreased and addition of the anti-oestrogens to ovarian tissue in vitro also decreased oestradiol synthesis. The results show that both compounds have a primary effect on ovarian oestradiol synthesis and probably exert a secondary effect on the development of the placenta.