LHRH AND THE LOSS OF FERTILITY IN AGING FEMALES

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Reproductive decline in female rats is characterized first by alterations in the pattern of the LH surge on proestrus and finally by complete absence of cyclic LH surges. Age related changes in LH secretory patterns in aging females are presumed to result ultimately from altered release of LHRH into the pituitary portal system. Very little information is currently available, however, regarding LHRH release in aging female rats. The series of experiments proposed here will characterize LHRH neurosecretion in aging female rats and they will determine whether 1) alterations in the patterns of LHRH release can be attributed solely to age related changes in the afferent input to the LHRH neurons or 2) alterations within the LHRH neurons themselves contribute to the loss of fertility. In experiment 1, push-pull perfusion will be utilized to characterize the pattern of LHRH secretion in middle-aged and young females on the day of proestrus or following ovariectomy and steroid administration. If alterations in amplitude or frequency of the pulsatile pattern of LHRH release are observed in the aging animals, attempts will be made to reverse these changes by administration of adrenergic agonists. In experiment 2, LHRH neurosecretion from isolated nerve terminals in the median eminence will be examined in vitro following non-specific (K+) and specific (PGE2, NE) stimulation. This approach will allow examination of possible age related changes in releasability of hypothalamic stores of LHRH apart from other age related changes, for example, in afferent input, that might also act to alter LHRH release in vivo. In experiment 3, the response of the LHRH system of middle-aged and young females will be observed following electrochemical stimulation (100MuA/60 sec) of the medial preoptic area. The results of experiment 3 will determine whether the LHRH system in the aging female rat maintains the capacity to respond to a stimulus causing increased demand for synthesis and release. Finally, immunocytochemical techniques will be employed in experiment 4 to investigate the anatomical basis for interaction between the catecholaminergic and LHRH systems. Co-localization of LHRH with the catecholamine synthesizing enzymes tyrosine hydroxylase and dopamine beta hydroxylase will be used to examine possible age related changes in afferent inputs tothe LHRH system.