Altered regulation of pituitary luteinizing hormone secretion by GnRH and inhibin in the aged persistent-estrous female rat

The physiologic regulation of pituitary LH secretion is under the direct control of hypothalamic GnRH as well as feedback control via ovarian steroid and peptide hormones. Changes within the hypothalamic-pituitary-ovarian axis during reproductive aging lead to the gradual attenuation and the eventual loss of cyclic LH release that is seen in the old persistent-estrous rat. In the following studies, we determined whether changes in the pituitary response to regulation by hypothalamic GnRH and/or ovarian inhibin could be involved in age-related deficits in LH release by examining the direct effect(s) of GnRH and inhibin on LH release in old persistent-estrous (PE) and young female rats using an in vitro pituitary cell culture system. Both pituitary LH content and LH release were significantly lower in PE pituitary cells compared to young pituitary cells. GnRH (10 ng/ml) significantly increased LH release above basal levels in young and PE pituitaries. However, the magnitude of LH release was significantly lower in PE pituitaries compared to young pituitaries. Treatment with recombinant inhibin (0.1, 1, or 5 ng/ml) did not significantly affect basal or GnRH-stimulated LH release from young rat pituitaries under our culture conditions. In contrast, there were significant decreases in the levels of both basal LH and GnRH-stimulated LH release from PE pituitaries after treatment with 1 or 5 ng/ml human recombinant inhibin, as well as with inhibin plus 10 ng/ml GnRH, respectively. These results suggest that there are significant changes in the pituitary response to GnRH and ovarian inhibin regulation that may lead to significant alterations in LH secretion during aging.