OVARY MEDIATES THE EFFECTS OF RU486 GIVEN DURING PROESTRUS ON THE DIESTRUS SECRETION OF LUTEINIZING-HORMONE IN THE RAT

The aim of these experiments was to study the action of proestrous aft ernoon follicular progesterone secretion on the preovulatory secretion of gonadotropins in the rat. Four-day-cycling rats were given 4 mg of the antiprogestagen RU486 in the morning of proestrus (Day 1), and it s effects on the pituitary function during diestrus were compared with those of RU486 given in the morning of estrus (Day 2). The pituitary function was assessed by measuring basal secretion of LH and FSH as we ll as the pituitary response to either estradiol benzoate (EB) (3 mu g /100 g BW at 1300 h on Day 3) or LHRH (100 ng/rat at 1200 h on Day 4). In all experiments, trunk blood was taken at 1300 h on Day 4 to measu re serum gonadotropin concentrations. In rats receiving an injection o f RU486 on estrus, the absence of only the diestrous progesterone acti ons increased basal serum concentrations of LH and decreased those of FSH, and, as in vehicle-treated controls, EB inhibited and LHRH stimul ated LH secretion. In contrast, the absence of both proestrous afterno on and diestrous progesterone actions (as characterized rats treated w ith RU486 on proestrus) antagonized the inhibitory effect of EB and se nsitized the pituitary to LHRH. These effects of RU486 on proestrus ar e ovary-dependent and eliminated by ovariectomy on metestrus. The incr eased ovarian secretion of testosterone and estradiol-17 beta during d iestrus does not mediate the effects of proestrus-administered RU486 o n pituitary function: no differences were found in the serum concentra tions of estradiol-17 beta in diestrus between the groups of rats trea ted with RU486, and administration of the antiandrogen flutamide (2 mg /rat at 0900 h on Days 2 and 3) did not reverse the effects of RU486 o n proestrus. In conclusion, the results suggest that in the absence of proestrous afternoon progesterone action, the ovaries of the 4-day-cy clic rat keep the pituitary gland in a state of low sensitivity to the inhibitory effects of estradiol and high sensitivity to the stimulato ry effects of LHRH. Moreover, the results suggest that the putative ov arian factors involved are factors other than progesterone, androgens, or estradiol-17 beta.