Reproductive endocrinology: Edited by David L. OliveMolecular causes of hypogonadotropic hypogonadismTopaloglu, Ali Kemala,b; Kotan, Leman DamlabAuthor Information aDepartment of Pediatric Endocrinology, Faculty of Medicine bDepartment of Biotechnology, Institute of Sciences, Cukurova University, Balcali, Adana, Turkey Correspondence to Dr A. Kemal Topaloglu, Department of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Balcali, Adana 01330, Turkey Tel: +90 322 338 77 17; fax: +90 322 338 77 17; e-mail: [email protected] Current Opinion in Obstetrics and Gynecology: August 2010 - Volume 22 - Issue 4 - p 264-270 doi: 10.1097/GCO.0b013e32833bb425 Buy Metrics Abstract Purpose of review What controls puberty remains largely unknown and current gene mutations account for only about one-third of the apparently genetic cases of idiopathic hypogonadotropic hypogonadism. Lately important developments have occurred in this field. Recent findings Substantial variation in clinical expression, from complete anosmia and hypogonadotropic hypogonadism to delayed puberty and normosmia, of the same Kallmann syndrome gene defects including in newer ones (FGF8 and CHD7) continues to be repeatedly observed. Digenic or oligogenic inheritance becomes another feature of Kallmann syndrome. Recent reports of mutations in TAC3 or TACR3 [encoding neurokinin B (NKB) and its receptor, NK3R, respectively] provided compelling evidence for the involvement of NKB signaling in puberty. This energized the field to understand the exact mechanism through which NKB signaling exerts its effects. With the important findings from these recent studies in association with the substantial data from kisspeptin studies in the last 6 years a sketch of GnRH pulse generator has emerged in which NKB signaling appears to play a key role. Summary Autozygosity mapping may continue helping identify the other genes including those upstream to the GnRH pulse generator in this complex and elusive developmental process. © 2010 Lippincott Williams & Wilkins, Inc.