Kallmann syndrome and idiopathic hypogonadotropic hypogonadism: The role of semaphorin signaling on GnRH neurons

Abstract

Idiopathic hypogonadotropic hypogonadism and Kallmann syndrome are rare genetic disorders characterized by isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) and delayed or absent puberty. Defective GnRH neuron migration during development or secretion of mature GnRH neurons secondary to molecular defects in several key developmental and neuroendocrine pathways are thought to be the primary causes of these disorders. Recent studies have highlighted the importance of semaphorins and their receptors in this system, by showing that these molecules play distinct roles during the development and plasticity of these neurons. Accordingly, mutations in the semaphoring-signaling pathway genes have been found in patients affected by IGD, underlying the importance of semaphorin-mediated signaling pathways in the neuroendocrine axis that control reproduction.

Keywords: GnRH neurons; Hypogonadotropic hypogonadism; Hyposmia; Kallmann syndrome; Mutations; Oligogenicity; Semaphorins.