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The Journal of Neuroscience, April 22, 2009, 29(16):5240-5250; doi:10.1523/JNEUROSCI.0405-09.2009

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Behavioral/Systems/Cognitive
The Ventral Premammillary Nucleus Links Fasting-Induced Changes in Leptin Levels and Coordinated Luteinizing Hormone Secretion

Jose Donato Jr,1,2 Renata J. Silva,1 Luciane V. Sita,1 Syann Lee,2 Charlotte Lee,2 Sílvia Lacchini,1 Jackson C. Bittencourt,1 Celso R. Franci,3 Newton S. Canteras,1 and Carol F. Elias1,2

1Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo 05508-900, Brazil, 2Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, and 3Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil

Correspondence should be addressed to Dr. Carol F. Elias, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Y6–220 Dallas, TX 75390. Email: carol.elias{at}utsouthwestern.edu

Physiological conditions of low leptin levels like those observed during negative energy balance are usually characterized by the suppression of luteinizing hormone (LH) secretion and fertility. Leptin administration restores LH levels and reproductive function. Leptin action on LH secretion is thought to be mediated by the brain. However, the neuronal population that mediates this effect is still undefined. The hypothalamic ventral premammillary nucleus (PMV) neurons express a dense concentration of leptin receptors and project to brain areas related to reproductive control. Therefore, we hypothesized that the PMV is well located to mediate leptin action on LH secretion. To test our hypothesis, we performed bilateral excitotoxic lesions of the PMV in adult female rats. PMV-lesioned animals displayed a clear disruption of the estrous cycle, remaining in anestrus for 15–20 d. After apparent recovery of cyclicity, animals perfused in the afternoon of proestrus showed decreased Fos immunoreactivity in the anteroventral periventricular nucleus and in gonadotropin releasing hormone neurons. PMV-lesioned animals also displayed decreased estrogen and LH secretion on proestrus. Lesions caused no changes in mean food intake and body weight up to 7 weeks after surgery. We further tested the ability of leptin to induce LH secretion in PMV-lesioned fasted animals. We found that complete lesions of the PMV precluded leptin stimulation of LH secretion on fasting. Our findings demonstrate that the PMV is a key site linking changing levels of leptin and coordinated control of reproduction.


Received Jan. 26, 2009; revised March 21, 2009; accepted March 22, 2009.

Correspondence should be addressed to Dr. Carol F. Elias, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Y6–220 Dallas, TX 75390. Email: carol.elias{at}utsouthwestern.edu






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