The semaphorin proteins are among the best-studied families of guidance cues, contributing to morphogenesis and homeostasis in a wide range of tissue types. Recently there has been increasing emphasis on research to determine the potential influence of semaphorins on the development and homeostasis of hormone systems and how circulating reproductive hormones regulate their expression and functions.

This talk focuses on recent advances in our understanding of the molecular mechanisms underlying the effects of semaphorins on the motility, survival, and axonal plasticity of unique neurons that secrete gonadotropin-releasing hormone (GnRH), which are essential for the acquisition and maintenance of reproductive competence in all vertebrates. During embryonic development, GnRH neurons originate in the nasal placode and migrate into the forebrain. Alterations either in the development of this system or in the secretion of GnRH are associated with hypogonadotropic hypogonadism (HH) in humans, a condition characterized by a reduction or failure of sexual competence. Unraveling the genetic pathways involved in the regulation of GnRH system development is crucial to understanding the basis of its pathogenesis in human reproductive disorders and formulating novel therapies. In a translational approach, this talk will present novel distinct genetic evidence showing that insufficient semaphorin signaling contributes to some forms of reproductive disorders in humans.

Furthermore, some emphasis will be put on some recent evidences indicating that semaphorins expression persists during adulthood in hypothalamic median eminence, where they play an important role in the plasticity of the neuroendocrine systems that defend homeostatic set points to enable the survival of individuals and species.

The identification of semaphorins and their associated receptors as participants in both the development and functional plasticity of hormone systems creates new avenues of investigation in endocrinology and neuroendocrinology.