Gruenewald D A, Naai M A, Marck B T, Matsumoto A M
Gerontology Research, Education, and Clinical Center, Veterans Administration Medical Center, Seattle, Washington 98108.
Endocrinology. 1994 Jun;134(6):2383-9. doi: 10.1210/endo.134.6.8194464.
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.
神经肽Y（NPY）被认为可调节生殖功能和食物摄入。NPY神经元活动受性类固醇调节，且NPY分泌随衰老而下降。我们推测，衰老导致NPY分泌减少是由于NPY基因表达降低，且这种降低与睾丸反馈无关。为验证这一假设，我们比较了假手术组和去势组的年轻（3个月大）、中年（13个月大）和老年（23个月大）雄性挪威棕色（BN）大鼠的弓状核（ARC）前体NPY（ppNPY）mRNA水平（通过原位杂交测定）和血清睾酮水平（通过放射免疫分析测定）。杂交面积和平均光密度（OD）用作ARC ppNPY mRNA含量的指标。在假手术组大鼠中，ppNPY mRNA杂交面积和OD均随衰老而逐渐降低，而血清睾酮水平仅在老年大鼠中降低，中年和年轻大鼠中未降低。在去势组大鼠中，ppNPY mRNA杂交面积也随衰老而显著降低，尽管OD没有明显变化。去势组大鼠的ppNPY mRNA杂交面积低于完整的年轻和中年大鼠，而OD不受去势影响。此外，衰老和去势对ppNPY mRNA水平的影响并不局限于ARC的特定区域。我们得出结论，在雄性BN大鼠中，ARC的NPY基因表达随衰老而降低，与睾丸反馈的影响无关。NPY合成能力的这种降低可能导致衰老过程中生殖功能和食物摄入的改变。
