title: Genetics and hypogonadotrophic hypogonadism.
abstract: Hypothalamic pulsatile gonadotrophin-releasing hormone secretion, stimulating pituitary gonadotrophin secretion, is essential for adult reproductive function. This neuroendocrine drive to the reproductive axis is critically dependent on a sequence of developmental events in utero. During early foetal life, gonadotrophin-releasing hormone neurones migrate from the nasal placode to the medial basal hypothalamus where gonadotrophin-releasing hormone can be transported down portal vessels to the anterior pituitary. Gonadotrophin-releasing hormone secretion is active fleetingly neonatally but soon becomes quiescent throughout childhood. At the time of puberty activation of gonadotrophin-releasing hormone secretion reawakens the hypothalamic pituitary-gonadal axis and secondary sexual maturation is triggered. Any disruption in gonadotrophin-releasing hormone secretion will result in hypogonadotrophic hypogonadism. The clinical manifestations of this become apparent with secondary sexual maturation. Genetic mutations have been identified in a minority of cases. These include Kallmann syndrome, adrenal hypoplasia congenital, gonadotropin-releasing hormone receptor and luteinizing hormone or follicle-stimulating hormone beta-subunit gene mutations. The importance of these discoveries is important not only in relation to the conditions that result, but also for our better understanding of normal reproductive function.
authors.affiliation: Department of Endocrinology, Manchester Royal Infirmary, Manchester, UK. Catherine.j.hay@man.ac.uk
authors.forename: Cathy
authors.initials: C
authors.lastname: Hay
authors.forename: Frederick
authors.initials: F
authors.lastname: Wu
mesh_terms: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D007986:Luteinizing Hormone / Q000235:genetics; D009154:Mutation; D011966:Receptors, LHRH / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D011966:Receptors, LHRH; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone