Département Génétique et Reproduction, CHU de Caen. F 14033, EA 2608 –USC INRA- Université de Caen. F 14032
As a major actor of the brain-pituitary-gonad axis, GnRH has received considerable attention. GnRH gene encodes for a 92 aminoacid precursor protein which is proteolytically processed to generate GnRH and GAP. The corresponding neurons develop from the olfactory epithelium and migrate into the fore brain during embryogenesis to establish connections with the median eminence. GnRH appears as very ancient peptide. However, all vertebrates possess a second GnRH system, expressing a variant known as chicken GnRH II whose function are still under debate. GnRH secretion is modulated by different factors mainly GnRH itself, sex-steroides, leptine as well as other factors released by glial cells that can modulate the direct access of GnRH neuroendocrine terminals to the vascular wall. A crucial role in GnRH secretion has been recently assigned to a new hypothalamic signalling pathway, which involves the G-protein-coupled receptor GPR54 and its natural ligands, the kisspeptine product of the KiSS-1 gene. The action of GnRH in the anterior pituitary gland are mediated by a G protein-coupled receptor (GnRH-R). Hypogonadotropic hypogonadism (HH) results from impaired secretion or action of GnRH. Abnormality in the migratory processes of the GnRH neurones with the olfactory neurons explains the association of the HH with anosmia. Loss of function mutation of GnRH-R as well as GPR54 are associated with isolated HH.