Leptin-deficient mice recapitulate human phenotypes; however, it is not clear how leptin and leptin signaling impact the reproductive axis.
In this issue of the Journal of Clinical Investigation, Vincent Prevot and colleagues at INSERM U837 evaluated leptin deficient animals and determined that leptin acts directly on neurons in the preoptic region of the hypothalamus that synthesize nitric oxide to regulate peripheral levels of leutinizing hormone (LH), which is essential for reproduction.
Administration of leptin increased neuronal production of nitric oxide synthase, while deletion or pharmacological inhibition of NOS blocked leptin-induced LH release in mice.
Mathematical models indicated that leptin action in the preoptic region leads to a build-up of NO that reaches a level that is critical for the induction and release of gonadotropin-releasing hormone (GnRH) and subsequent LH secretion by the pituitary gland.
This study demonstrates that leptin communicates the status of peripheral energy stores to GnRH-releasing neurons via the preoptic hypothalamus to regulate fertility.