Pituitary gonadotropin-releasing hormone receptors during gonadotropin surges in ovariectomized-estradiol-treated rats.

In intact cycling rats, the number of pituitary GnRH receptors varies markedly during the estrous cycle. Concentrations are maximal on diestrus and early proestrus, before falling rapidly for a brief period immediately before the preovulatory gonadotropin surge. In this study we investigated whether dynamic changes in ovarian steroids, pituitary hormones, and GnRH itself, all of which are changing at the time of the surge, play a role in the acute transient down-regulation of the pituitary GnRH receptors. We used the ovariectomized-estradiol-treated female rat as a model, as these animals exhibit daily gonadotropin surges at a predictable time of the day and also allow studies in a situation where concentrations of ovarian steroids are stable. The pituitary GnRH binding capacity (GnRH-BC) was measured using the analog D-Ala6des Gly10-GnRH ethylamide as ligand. GnRH-BC was stable between 0900-1530 h [range, 288 +/- 29 to 262 +/- 33 fmol protein (mean +/- SE)] and fell abruptly to 123 +/- 17 fmol/mg at 1630 h, before returning to the initial level by 1730 h. This abrupt fall in GnRH-BC preceded the afternoon gonadotropin surge and was similar in timing, magnitude, and duration to that observed in intact cycling rats. Serum PRL decreased from peak levels at 1630 h, coincident with the fall in GnRH-BC, before rebounding at 1730 h. Pentobarbital given at 1400 h abolished both the gonadotropin surge and the acute fall in GnRH-BC, but did not change serum PRL levels, suggesting that PRL is not causally related to the fall in GnRH-BC. The stable morning levels of GnRH-BC were not reduced after iv injections of LH, FSH, or both hormones despite elevations in serum gonadotropins to concentrations greater than those seen during the afternoon surge. Additionally, multiple iv injections of GnRH at 30- or 10-min intervals did not decrease the stable morning levels of GnRH-BC, although serum LH and FSH were markedly elevated. The data suggest that dynamic fluctuations in ovarian steroids, gonadotropins, PRL, and GnRH are not causally related to the acute transient reduction of pituitary GnRH receptors before the afternoon gonadotropin surge. These results also suggest that another hypothalamic or pituitary factor(s) is involved in the acute regulation of GnRH receptors, and the ovariectomized-estradiol-treated rat appears to be a good model for the elucidation of the factor(s) involved.