AGE-RELATED DECREASE IN NEUROPEPTIDE-Y GENE-EXPRESSION IN THE ARCUATENUCLEUS 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 N PY secretion declines with aging. We hypothesized that reduced NPY sec retion with aging is due to decreased NPY gene expression,and that thi s decrease is independent of testicular feedback. To test this hypothe sis, arcuate nucleus (ARC) prepro-NPY (pphNPY) mRNA levels, determined by in situ hybridization, and serum testesterone levels, determined b y RIA, were compared in sham-operated and orchidectomized young (13 mo nths old), middle-aged (13 months old), and old (23 months old) male B rown 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 progressivel y with aging, whereas serum testosterone levels were decreased only in old, not in middle-aged or young, rats. In orchidectomized rats, ppNP Y mRNA hybridization area also decreased significantly with aging, alt hough OD did not change significantly. The ppNPY mRNA hybridization ar ea was lower in orchidectomized than in intact young and middle-aged r ats, whereas OD was unchanged by orchidectomy. Furthermore, the effect s 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, AR C NPY gene expression is decreased with aging independently of the eff ects of testicular feedback. This reduction in NPY synthetic capacity may contribute to altered reproductive function and food intake with a ging.