Molecular causes of hypogonadotropic hypogonadism.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
Autozygosity mapping may continue helping identify the other genes including those upstream to the GnRH pulse generator in this complex and elusive developmental process.
Topaloglu
Ali Kemal
AK
Department of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, Balcali, Adana 01330, Turkey. ktopaloglu@cu.edu.tr
Kotan
Leman Damla
LD
D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D059648:Kisspeptins; D008297:Male; D051379:Mice; D015287:Neurokinin B / Q000235:genetics; D010913:Pituitary-Adrenal System / Q000502:physiology; D011627:Puberty / Q000502:physiology*; D011628:Puberty, Delayed / Q000235:genetics* / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D015287:Neurokinin B