Administration of antiprogestagens (2 mg/day) to female rats for 21 days induces high serum prolactin levels. These levels stimulate luteal progesterone production and an increase in ovarian weight. Compared with RU486 (mifepristone) the increase in prolactin is less after treatment with ZK299 (onapristone), an antiprogestagen with lower antiglucocorticoid activity. To study whether cyclic ovulations occur in rats treated with antiprogestagens, 5-day cyclic rats were given daily injections of RU486 or ZK299 (2 mg) from metoestrus (day 1) to pro-oestrus. This treatment advanced the forthcoming ovulation by 1 day; however, the ovulation rate was low. Injection of 10 IU human chorionic gonadotrophin on the afternoon of pro-oestrus (day 3) increased the ovulation rate, but not to the level found in oil-treated rats.
Serum LH concentrations measured from metoestrus to oestrus at 10.00 and 17.00 h were higher in antiprogestagen- than in oil-treated rats from day 2 (17.00 h) onwards. A low preovulatory LH surge was found in antiprogestagen-treated rats on the after-noon of pro-oestrus (day 3). Ovarian histology at the day of oestrus (day 4) confirmed the presence of a low LH surge as, besides ruptured follicles, unruptured follicles with dispersion of cumulus cells were present. The pro-oestrous surge of prolactin was also advanced by 24 h. The magnitude, however, was not different from that in oil-treated rats at day 4.
In conclusion, daily administration of antiprogestagens to 5-day cyclic rats results in increased basal levels of serum LH and advancement of the preovulatory surge of prolactin and LH by 1 day. The ovulatory response is low due to the low pre-ovulatory surge of LH and to a reduced ability of preovulatory follicles to respond to LH.
Journal of Endocrinology (1991) 129, 423–429