GnRH neuronal development: insights into hypogonadotrophic hypogonadism

Pulsatile secretion of the hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) regulates activity of the pituitary-gonadal reproductive axis. Defects of this neuroendocrine axis necessarily result in hypogonadotrophic hypogonadism. In many vertebrate species studied,the main population of GnRH neurones originates extracranially within the olfactory system. In humans, both olfactory and GnRH systems are affected in Kallmann's syndrome-resulting in isolated hypogonadotrophic hypogonadism (IHH) combined with anosmia (loss of sense of smell). Familial IHH is also caused by other genetic conditions, which prevent GnRH from activating luteinizing hormone/follicle-stimulating hormone release from pituitary gonadotrophs. However, many cases of IHH have no defined chromosomal abnormality and, in the absence of pedigree analysis, studying the biological mechanisms controlling migration of GnRH neurones through the olfactory system into the developing central nervous system might reveal additional genetic pathways that play a role in the pathogenesis of IHH.