Genetics and hypogonadotrophic hypogonadism.
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.
Hay
Cathy
C
Department of Endocrinology, Manchester Royal Infirmary, Manchester, UK. Catherine.j.hay@man.ac.uk
Wu
Frederick
F
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*
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