Age-related decrease in neuropeptide-Y gene expression in the arcuate nucleus of the male rat brain is independent of testicular feedback.

Neuropeptide-Y (NPY) is thought to modulate reproductive function and food intake. NPY neuronal activity is modulated by sex steroids, and NPY secretion declines with aging. We hypothesized that reduced NPY secretion with aging is due to decreased NPY gene expression, and that this decrease is independent of testicular feedback. To test this hypothesis, arcuate nucleus (ARC) prepro-NPY (ppNPY) mRNA levels, determined by in situ hybridization, and serum testosterone levels, determined by RIA, were compared in sham-operated and orchidectomized young (3 months old), middle-aged (13 months old), and old (23 months old) male Brown Norway (BN) rats. Hybridization area and average optical density (OD) were used as indices of ARC ppNPY mRNA content. In sham-operated rats, both ppNPY mRNA hybridization area and OD decreased progressively with aging, whereas serum testosterone levels were decreased only in old, not in middle-aged or young, rats. In orchidectomized rats, ppNPY mRNA hybridization area also decreased significantly with aging, although OD did not change significantly. The ppNPY mRNA hybridization area was lower in orchidectomized than in intact young and middle-aged rats, whereas OD was unchanged by orchidectomy. Furthermore, the effects of aging and orchidectomy on ppNPY mRNA levels were not localized to a specific region of the ARC. We conclude that in the male BN rat, ARC NPY gene expression is decreased with aging independently of the effects of testicular feedback. This reduction in NPY synthetic capacity may contribute to altered reproductive function and food intake with aging.