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Evidence that hypothalamic neuropeptide Y secretion decreases in aged male rats: implications for reproductive aging.

The decrease in circulating testosterone and LH titer that occurs in aged male rats may in part be a consequence of decreased excitatory neurochemical signals that promote the episodic discharge of LHRH from the hypothalamus. In view of evidence that neuropeptide Y (NPY) stimulates the release and potentiates the action of LHRH on LH secretion, the present studies investigated age-related changes in the concentrations of NPY in individual hypothalamic nuclei and in the ability of hypothalamic tissues to release NPY in vitro. Compared with tissues of 2.5-month-old male rats, medial basal hypothalamic tissues of 13-month-old rats released significantly less NPY in response to K+ depolarization. In contrast, K+-evoked LHRH release from the same tissues was unimpaired. Aged male rats also exhibited markedly reduced concentrations of NPY in the median eminence and in the arcuate, medial preoptic, suprachiasmatic, paraventricular, dorsomedial, and ventromedial hypothalamic nuclei, which are sites of NPY perikarya and nerve terminal networks. These neurochemical changes occurred in association with decreased serum testosterone and LH levels. These findings demonstrate a widespread age-related decline in NPY levels and release in the hypothalamus, which may be responsible for the reduction in testosterone secretion and may contribute to the decline in reproductive function in aged male rats.