ABSENCE OF INCREASED NEUROPEPTIDE-Y NEURONAL-ACTIVITY BEFORE AND DURING THE LUTEINIZING-HORMONE (LH) SURGE MAY UNDERLIE THE ATTENUATED PREOVULATORY LH SURGE IN MIDDLE-AGED RATS

A large body of evidence suggests that the neuroendocrine axis plays a major role in the reproductive aging of female rats. Since increased hypothalamic neuropeptide Y (NPY) neurosecretion is crucial in the pre ovulatory LH discharge in young rats, we tested the hypothesis that di minution in the preovulatory LH. surge in middle-aged (MA) rats may be due to altered neurosecretory activity in NPYergic neurons. In Exp 1, we examined NPY levels in six micro-dissected hypothalamic nuclei, in cluding median eminence (ME), arcuate nucleus (ARC), and medial preopt ic area (MPOA), at 1000, 1200, 1400, 1600, 1800, 2000, or 2200 h on th e day of proestrus in young (2.5- to 3-month old) and MA (7- to 9-mont h old regularly cycling rats. At 1000 h, ME NPY levels in young rats w ere significantly lower than those in MA rats. In young rats, the ME N PY levels were significantly increased at 1400 h before the LII surge in the afternoon and thereafter decreased progressively during the int erval of the LH surge. In MA rats, however, ME NPY levels decreased in the afternoon in association with an attenuated LH surge. In addition , in the ARC and MPOA, the other hypothalamic sites associated with in duction of LH surge, NPY levels increased before and during the LH sur ge in young rats, no change in NPY levels in these nuclei was observed in association with the attenuated LH surge in MA rats. Also, NPY lev els in the ARC and MPOA during the afternoon were significantly lower in MA compared with those in young animals. These results demonstrated the absence of an antecedent increase in NPY levels, specifically in the ME and ARC, during the afternoon of proestrus in MA animals. In a second experiment, we evaluated whether the absence of dynamic changes in NPY levels in the ME and ARC in MA rats was due to altered hypotha lamic NPY gene expression. Regularly cycling young (2.5- to 3-month-ol d) and MA (8- to 10-month-old) rats were killed at 1000, 1200, 1400, 1 600, 1800, 2000, or 2200 h on the day of proestrus. The medial basal h ypothalamus was processed for prepro-NPY messenger RNA (mRNA) measurem ent by ribonuclease protection assay. In young rats, prepro-NPY mRNA l evels were significantly increased at 1200 h and remained elevated thr oughout the afternoon. In contrast, in MA rats prepro-NPY mRNA levels remained unchanged before and during the attenuated LH surge. These re sults clearly indicate that the augmentation in NPY neuronal activity before and during the LH surge seen in young rats fails to manifest it self in middle-aged rats. As hypothalamic NPY participates in the indu ction of LHRH surge, our results suggest that reduced LHRH and LH surg es in MA rats may be due to diminution in NPY secretion in these anima ls.