ALTERED REGULATION OF PITUITARY LUTEINIZING-HORMONE SECRETION BY GNRHAND INHIBIN IN THE AGED PERSISTENT-ESTROUS FEMALE RAT

The physiologic regulation of pituitary LH secretion is under the dire ct control of hypothalamic GnRH as well as feedback control via ovaria n steroid and peptide hormones. Changes within the hypothalamic-pituit ary-ovarian axis during reproductive aging lead to the gradual attenua tion and the eventual loss of cyclic LH release that is seen in the ol d persistent-estrous rat. In the following studies, we determined whet her changes in the pituitary response to regulation by hypothalamic Gn RH 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 L H release in old persistent-estrous (PE) and young female rats using a n in vitro pituitary cell culture system. Both pituitary LH content an d LH release were significantly lower in PE pituitary cells compared t o young pituitary cells. GnRH (10 ng/ml) significantly increased LH re lease above basal levels in young and PE pituitaries. However, the mag nitude of LH release was significantly lower in PE pituitaries compare d to young pituitaries. Treatment with recombinant inhibin (0.1, 1, or 5 ng/ml) did not significantly affect basal or GnRH-stimulated LH rel ease from young rat pituitaries under our culture conditions. In contr ast, there were significant decreases in the levels of both basal LH a nd 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 result's suggest that there are sig nificant changes in the pituitary response to GnRH and ovarian inhibin regulation that may lead to significant alterations in LH secretion d uring aging.