Inappropriate ovarian feedback in basal gonadotropin secretion in 4-day cyclic rat treated with mifepristone: role of endogenous estradiol.

Administration of the antiprogesterone RU486 to 4-day cyclic rats from metestrus onwards resulted in a dissociation of basal LH and FSH secretion and ovariectomy abolished this effect of RU486. Since RU486 also induces abnormally high concentrations of testosterone without affecting estradiol concentrations during the diestrous phase, we have studied the involvement of androgen or estrogen in RU486-dissociated gonadotropin secretions. Ovariectomized- (OVX) or sham-OVX rats at 08:00 h in metestrus were injected with RU486 (2 mg) or vehicle (0.2 ml) at 08:00 and 17:00 h in metestrus (day 1) and diestrus (day 2). Also, OVX-and sham-OVX rats injected with RU486 or oil were, in addition, treated with the antiandrogen flutamide and/or the antiestrogen tamoxifen (1 mg/0.2 ml) at 08:00 and 17:00 on days 1 and 2. The serum concentrations of LH and FSH were determined at 08:00 and 17:00 h on days 1 and 2 and at 08:00 h on day 3. OVX completely reversed the effects of RU486 on basal gonadotropin secretions while flutamide treatment affected neither LH nor FSH in any of the groups studied. On the contrary, tamoxifen treatment in RU486-injected rats reduced the LH concentrations to the levels found in OVX-rats and increased FSH concentrations to the levels in sham-OVX rats. Since the doses of flutamide and tamoxifen used block the action of androgens and estrogens, respectively, the results of this study evidence that endogenous estradiol in the absence of the effects of progesterone at both hypothalamus-pituitary and ovary levels stimulates LH and inhibits FSH secretion during the low secretion rate of gonadotropins in the rat.