title: Neurokinin B and its receptor in hypogonadotropic hypogonadism.
abstract: The hypothalamus integrates multiple environmental and developmental cues relevant to reproductive function, serving to transduce these into a pulsatile output of gonadotropin-releasing hormone (GnRH). Although neuroanatomical and physiological studies have yielded key clues about the functional organisation of the so-called 'GnRH pulse generator', only in the last decade have the molecular components of the circuitry upstream from GnRH begun to be elucidated. A major contributor to this has been human genetics, through identification of mutations causing isolated hypogonadotropic hypogonadism (IHH) without developmental defects. The greatest success of this approach was the finding in 2003 that mutations of KISS1R cause IHH, producing a quantum leap in understanding of regulation of GnRH secretion, and energising the field. New evidence has now emerged that loss of function of neurokinin B (NKB) or its receptor, the neurokinin-3 receptor, produces IHH of similar severity to that caused by KISS1R mutations in humans. Preliminary evidence suggests that the role of NKB in reproductive function differs significantly between humans and rodents, posing challenges for future studies. We review the human genetics of NKB and its receptor, and discuss the future work required to elucidate their precise role in the regulation of human GnRH secretion.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Semple
authors.forename: A Kemal
authors.initials: AK
authors.lastname: Topaloglu
mesh_terms: D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D015287:Neurokinin B / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D018042:Receptors, Neurokinin-3 / Q000235:genetics*; D018039:Receptors, Tachykinin / Q000235:genetics; D012098:Reproduction / Q000502:physiology; D015320:Tachykinins / Q000235:genetics
chemical_list: D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; D015287:Neurokinin B