title: The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion.
abstract: 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.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo 05508-900, Brazil.
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
authors.forename: Renata J
authors.initials: RJ
authors.lastname: Silva
authors.forename: Luciane V
authors.initials: LV
authors.lastname: Sita
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lee
authors.forename: Sílvia
authors.initials: S
authors.lastname: Lacchini
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
authors.forename: Celso R
authors.initials: CR
authors.lastname: Franci
authors.forename: Newton S
authors.initials: NS
authors.lastname: Canteras
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
mesh_terms: D000818:Animals; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005260:Female; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism* / Q000473:pathology
chemical_list: D020738:Leptin; D007986:Luteinizing Hormone