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Neuropeptide Y Gene Expression Is Increased in the Hypothalamus of Older Women

Departments of Pathology, Cell Biology and Anatomy, and Neurology (C.M.E., S.J.K., T.S.-G., N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724; and Department of Pathology (M.L.V.), Section of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Address all correspondence and requests for reprints to: Naomi E. Rance, M.D., Ph.D., Department of Pathology, University of Arizona College of Medicine, 1501 North Campbell Avenue, Tucson, Arizona 85724. E-mail: nrance{at}u.arizona.edu.

Neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the infundibular (arcuate) nucleus of the hypothalamus are part of a reciprocal circuit regulating reproduction and energy balance. Based on studies showing an age-related decrease in POMC mRNA, we hypothesized that NPY gene expression would increase in older women. In situ hybridization was used to compare NPY mRNA levels between young (premenopausal) and older (postmenopausal) women. We also measured NPY gene expression in intact and ovariectomized young cynomolgus monkeys. We report a significant increase (100%) in the numbers of autoradiographic grains/NPY neuron in the retrochiasmatic area and infundibular nucleus of older women. NPY mRNA was correlated with subject age and inversely proportional to the number of POMC neurons previously counted in the same subjects. In contrast, there was no difference in hypothalamic NPY mRNA in intact vs. ovariectomized monkeys. These data show that aging in women is associated with increased NPY gene expression and suggest that the functional relationship between NPY and POMC neurons demonstrated in other species also exists in the human. Our studies of intact and ovariectomized monkeys suggest that the increase in NPY mRNA in older women is due to factors other than the ovarian failure of menopause.

This work was supported by NIH National Institute on Aging Grant AG-09214. C.M.E. was supported by a grant to the Undergraduate Biology Research Program from the Howard Hughes Medical Institute. T.S.-G. was a recipient of a predoctoral fellowship from the Robert S. Flinn Biomedical Research Initiative.

Abbreviations: NKB, Neurokinin B; NPY, neuropeptide Y; OVX, ovariectomized; POMC, proopiomelanocortin.

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