Sirt1 gene encodes an NAD+-dependent histone deacetylase. Hypogonadotropic hypogonadism is associated with energy restriction or may be inherited as congenital hypogonadotropic hypogonadism (CHH). CHH associated with a loss in sense of smell (anosmia) is called Kallmann syndrome. Kallmann syndrome is also associated with mutations in a group of genes that impact FGF8 function. In the recent studies by Di Sante et al., Sirt1-/- mice showed a hypogonadotropic hypogonadism due to failed gonadotropin-releasing hormone neuronal migration (GnRH). The Sirt1 catalytic function was required for GnRH neuronal migration via binding and deacetylating cortactin in an FGF8/FGFR1-dependent manner. The effect of Sirt1 on the hormonal status of Sirt1-/- mice, mediated via defective GnRH neuronal migration, links energy metabolism directly to the hypogonadal state. This review focuses on the biological function of Sirt1 in the brain and the mechanism by which Sirt1 promotes GnRH neuronal migration into the brain from the vomeronasal organ to the forebrain and how the failure of this migration leads to the development of Kallmann syndrome.
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