ALTERATIONS IN GONADOTROPIN-RELEASING HORMONE-DEPENDENT GONADOTROPIN-SECRETION IN RATS WITH POLYCYSTIC OVARIES

A single injection of estradiol valerate (EV) to adult female rats induces a persistent anovulatory polycystic ovarian (PCO) condition. During the 8-20-wk interval following EV treatment, this condition is associated with a selective compromise of LH release, decreased pituitary content of LH, and decreased GnRH-stimulated LH secretion. A marked increase in mean plasma concentrations of LH and enhanced LH response to GnRH occur after 20 wk post-EV treatment. Despite this apparent improvement, the PCO condition remains unchanged. The present study was undertaken to elucidate the underlying causes for these spontaneous improvements in LH parameters. We reasoned that these changes may be the result of alterations in 1) pituitary GnRH receptor levels; or 2) the mode of LH secretion, i.e. GnRH-dependent versus GnRH-independent; or 3) post-GnRH receptor events. Hence, we assessed pituitary GnRH receptor concentration as well as the pituitary content of LH and FSH in rats with PCO of 9 wk and 22 wk duration. To examine the possibility of a change in the mode of LH secretion, we examined the effects of in vivo suppression of LH secretion by treatment with a GnRH antagonist [N-Ac-D-Nal1, D-Phe2,3, D-Arg6, Phe7, D-Ala10]-GnRH (GnRH-ANTAG) in the same groups of animals. Mean pituitary weights were greater in the 9-wk-PCO than in the 22-wk-PCO animals. The pituitary concentration of GnRH receptors (on either a weight or milligram pituitary-membrane protein basis) was similar in the 9-wk- and 22-wk-PCO animals. Pituitary LH and FSH contents, however, were significantly higher (5-fold and 2-fold, respectively) in 22-wk-PCO rats compared to the 9-wk-PCO animals. Significant suppression of mean plasma LH concentrations was obtained for both groups following treatment with either 3 or 30-mu-g GnRH- ANTAG/rat. The concentration of LH achieved in the antagonist-treated animals was similar for both the 9-wk- and 22-wk-PCO groups. Thus the increased plasma LH concentrations characteristic of the 22-wk-PCO rats are completely GnRH-dependent. In both groups of animals, plasma LH concentrations had returned to their characteristic levels by 48 h after antagonist treatment. Our results indicate that the elevated plasma LH and enhanced pituitary sensitivity observed for the 22-wk-PCO rats are not the result of changes in pituitary GnRH receptor concentrations nor are they due to increased GnRH-independent LH secretion. We suggest that some post GnRH-receptor event(s) in the LH synthesis-secretion pathway is amplified in rats with PCO of long duration.