Altered pituitary responsiveness to gonadotropin- releasing hormone in middle-aged rats with 4-day estrous cycles

We employed a perifusion system to compare the GnRH responsiveness of pituitaries removed from young (3-6 months old) and middle-age (10-14 months old) female rats with 4-day estrous cycles in order to determine whether changes at this locus may contribute to alterations in LH secretion which precede a loss of regular estrous cycles. Pituitaries were removed and halved on each day of the 4-day cycle; one hemipituitary was retained for measurement (by RIA) of LH content. The second half was perifused for 2.5 h with medium 199 plus BSA, then stimulated for 6 h with 10(-7) M GnRH in medium 199 plus BSA. Results were as follows. 1) Within young and middle-aged groups, the magnitude of GnRH-stimulated LH release varied with stage of the estrous cycle (proestrus, diestrous day 2 greater than estrus, diestrous day 1). General patterns of LH release were similar between age groups; however, pituitaries removed from middle-aged females released significantly less LH on proestrus and diestrous day 1 than did those removed from young females. 2) The time required to reach maximal response to GnRH also varied with the estrous stage; response times were shortest on proestrus and estrus in both age groups. The time to maximal response was significantly longer in the middle-aged vs. the young group on all days of the estrous cycle except diestrous day 2. 3) Within age groups, pituitary LH content varied with the estrous cycle in a pattern similar to that of GnRH responsiveness. Between groups, LH content in middle-age females was equivalent to or greater than that in young females on all days of the cycle. These results indicate that reduced pituitary responsiveness to GnRH may contribute to the delayed attenuated proestrous LH surge that precedes reproductive senescence in the female rat.