Ovary mediates the effects of RU486 given during proestrus on the diestrous secretion of luteinizing hormone in the rat

The aim of these experiments was to study the action of proestrous afternoon 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 its 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 well 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 measure serum gonadotropin concentrations. In rats receiving an injection of RU486 on estrus, the absence of only the diestrous progesterone actions increased basal serum concentrations of LH and decreased those of FSH, and, as in vehicle-treated controls, EB inhibited and LHRH stimulated LH secretion. In contrast, the absence of both proestrous afternoon and diestrous progesterone actions (as characterized rats treated with RU486 on proestrus) antagonized the inhibitory effect of EB and sensitized the pituitary to LHRH. These effects of RU486 on proestrus are ovary-dependent and eliminated by ovariectomy on metestrus. The increased ovarian secretion of testosterone and estradiol-17 beta during diestrus does not mediate the effects of proestrus-administered RU486 on pituitary function: no differences were found in the serum concentrations of estradiol-17 beta in diestrus between the groups of rats treated 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 on proestrus. In conclusion, the results suggest that in the absence of proestrous afternoon progesterone action, the ovaries of the 4-day-cyclic rat keep the pituitary gland in a state of low sensitivity to the inhibitory effects of estradiol and high sensitivity to the stimulatory effects of LHRH. Moreover, the results suggest that the putative ovarian factors involved are factors other than progesterone, androgens, or estradiol-17 beta.