Endocrine Abstracts

This talk summarizes recent studies analysing the contribution of specific guidance molecules named semaphorins in the development and adult function of gonadotropin-releasing hormone (GnRH) neurons. In vertebrates, the GnRH decapeptide regulates the secretion of luteinizing hormone and follicle stimulating hormone, which govern puberty onset, gametogenesis, and estrous cycling, from anterior pituitary gonadotropes. During embryonic development, these cells originate from the nasal placode and migrate to the hypothalamus apposed to olfactory-vomeronasal nerves.

Alterations either in the development of this system or in the secretion of GnRH are associated with reduction or failure of sexual competence. In order to understand the pathogenesis of human reproductive disorders, it is thus relevant identifying molecular pathways involved in the regulation of the GnRH system.

The semaphorin proteins are one of the largest families of guidance cues, contributing to morphogenesis and homeostasis in a wide range of tissue types, including the brain. During embryonic development, several semaphorins are expressed in the olfactory-vomeronasal system and along the GnRH migratory route, prompting several groups of research to study their eventual involvement in the proper development of the GnRH and olfactory systems.

In recent years several studies have started to shed light on the role of semaphorins in the motility, survival and axonal plasticity of GnRH neurons.

This talk will review some of these studies, which provided insight into the sophisticated molecular mechanisms that allow for the spatiotemporal control of the responsiveness to semaphorins of developing GnRH neurons. Genetic data are also presented to show that some forms of reproductive disorders in humans are associated with mutations in specific classes of semaphorin family members.

Finally, some emphasis will be put on some recent studies, which started to shed light on the molecular mechanisms responsible for the progression of the estrous cycle in rodents and suggest that this phenomenon relies on the antagonistic effects of two semaphorins whose expression in the median eminence is periodically influenced by circulating sex hormones.

Disclosure: This work was supported by the Institut National de la Sante et de la Recherche Medicale, Inserm, France (grant number U837), Agence Nationale de la Recherche, ANR, France (grant numbers ANR-2010-JCJC-1404 – 01 and ANR-14-CE12-0015-01 RoSes).