Endocrinology, Vol 134, 2367-2370, Copyright © 1994 by Endocrine Society

ARTICLES

Anorectic effects of estrogen may be mediated by decreased neuropeptide- Y release in the hypothalamic paraventricular nucleus

JJ Bonavera, MG Dube, PS Kalra and SP Kalra
Department of Physiology, University of Florida College of Medicine, Gainesville 32610-0244.

There is a considerable body of evidence to suggest that estrogen suppresses food intake and body weight gain by an action in the hypothalamus. However, the neurotransmitter/neuromodulator mediating the anorectic effects of estrogen are unknown. Neuropeptide-Y (NPY) is the most potent orexigenic signal known, and NPY-producing neurons in the hypothalamus concentrate 17 beta-estradiol (E2). In these studies we tested the hypothesis that estrogen-induced anorectic effects may be due to decreased NPY levels and release in hypothalamic sites previously implicated in the control of food intake. The results show that uninterrupted physiological levels of E2 in ovariectomized rats suppressed daily food intake and body weight gain. Evaluation of NPY concentrations in five hypothalamic sites showed that NPY levels were decreased selectively in the paraventricular nucleus (PVN) and neighboring perifornical nucleus of E2-treated rats. In contrast, concentrations of beta-endorphin, another less potent orexigenic peptide, were not changed by E2 in any hypothalamic site. In the next experiment, the effects of similar E2 treatment on NPY release in vitro from the PVN and ventromedial nucleus were studied in rats killed at the onset of the dark phase when food intake increases in conjunction with increased PVN NPY secretion. The results show that basal and KCl- induced NPY release were significantly decreased from the PVN of E2- treated compared to those in control rats. In contrast, both basal and KCl-induced NPY release from the ventromedial nucleus of E2-treated rats were similar to those in control rats. Collectively, these results show that estrogen suppresses NPY levels and release selectively from the PVN. As NPY levels and release in the PVN have been shown to be highly correlated with appetite status, and the PVN is one of the important sites of NPY action, these findings imply that the anorectic effects of estrogen may be mediated by decreased NPY release from the PVN NPY innervations.

This article has been cited by other articles:

				T. A. Roepke, A. Malyala, M. A. Bosch, M. J. Kelly, and O. K. Ronnekleiv Estrogen Regulation of Genes Important for K+ Channel Signaling in the Arcuate Nucleus Endocrinology, October 1, 2007; 148(10): 4937 - 4951. [Abstract] [Full Text] [PDF]

				D. Titolo, F. Cai, and D. D. Belsham Coordinate Regulation of Neuropeptide Y and Agouti-Related Peptide Gene Expression by Estrogen Depends on the Ratio of Estrogen Receptor (ER) {alpha} to ER{beta} in Clonal Hypothalamic Neurons Mol. Endocrinol., September 1, 2006; 20(9): 2080 - 2092. [Abstract] [Full Text] [PDF]

				C. Acuna-Goycolea, N. Tamamaki, Y. Yanagawa, K. Obata, and A. N. van den Pol Mechanisms of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Inhibition of Identified Green Fluorescent Protein-Expressing GABA Neurons in the Hypothalamic Neuroendocrine Arcuate Nucleus J. Neurosci., August 10, 2005; 25(32): 7406 - 7419. [Abstract] [Full Text] [PDF]

				R. Meli, M. Pacilio, G. M. Raso, E. Esposito, A. Coppola, A. Nasti, C. Di Carlo, C. Nappi, and R. Di Carlo Estrogen and Raloxifene Modulate Leptin and Its Receptor in Hypothalamus and Adipose Tissue from Ovariectomized Rats Endocrinology, July 1, 2004; 145(7): 3115 - 3121. [Abstract] [Full Text] [PDF]

				F. Catalina, L. Milewich, V. Kumar, and M. Bennett Dietary Dehydroepiandrosterone Inhibits Bone Marrow and Leukemia Cell Transplants: Role of Food Restriction Experimental Biology and Medicine, December 1, 2003; 228(11): 1303 - 1320. [Abstract] [Full Text] [PDF]

				F. Catalina, S. G. Speciale, V. Kumar, L. Milewich, and M. Bennett Food Restriction-like Effects of Dietary Dehydroepiandrosterone. Hypothalamic Neurotransmitters and Metabolites in Male C57BL/6 and (C57BL/6 DBA/2)F1 Mice Experimental Biology and Medicine, March 1, 2001; 226(3): 208 - 215. [Abstract] [Full Text]

				M. Campbell-Thompson, G. Y. Lauwers, K. K. Reyher, J. Cromwell, and K. T. Shiverick 17{beta}-Estradiol Modulates Gastroduodenal Preneoplastic Alterations in Rats Exposed to the Carcinogen N-Methyl-N'-Nitro-Nitrosoguanidine Endocrinology, October 1, 1999; 140(10): 4886 - 4894. [Abstract] [Full Text]

				S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight Endocr. Rev., February 1, 1999; 20(1): 68 - 100. [Abstract] [Full Text]

				S. F. Leibowitz, A. Akabayashi, J. T. Alexander, and J. Wang Gonadal Steroids and Hypothalamic Galanin and Neuropeptide Y: Role in Eating Behavior and Body Weight Control in Female Rats Endocrinology, April 1, 1998; 139(4): 1771 - 1780. [Abstract] [Full Text] [PDF]