期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 6, 页码 2550-2559出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI65928
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资金
- NEUROBESE International Associated Laboratory (France)
- Fondation pour la Recherche Medicale [DEQ20130326524]
- Agence National pour la Recherche (France) [ANR-09-BLAN-0267]
- EUFP7 Integrated Project [266408]
- Biotechnology and Biological Sciences Research Council [BB/F01936X/1]
- NIH [DK84142]
- University of Lille 2
- BBSRC [BB/K003178/1, BB/F01936X/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K003178/1, BB/F01936X/1] Funding Source: researchfish
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0267] Funding Source: Agence Nationale de la Recherche (ANR)
The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonad otropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalatno-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.
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