ORIGINAL ARTICLE The Effects of Neurokinin B upon Gonadotrophin Release in Male Rodents M. P. Corander,* B. G. Challis,* E. L. Thompson, Z. Jovanovic,* Y. C. Loraine Tung,* D. Rimmington,* I. T. Huhtaniemi,à K. G. Murphy,  A. K. Topaloglu,§ G. S. H. Yeo,* S. O’Rahilly,* W. S. Dhillo, R. K. Semple* and A. P. Coll* *University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Cambridge, UK.  Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, UK. àDepartment of Reproductive Biology, Imperial College London, London, UK. §Department of Pediatric Endocrinology and Metabolism, Faculty of Medicine, Cukurova University, Balcali, Adana, Turkey. The tachykinins are a family of structurally related peptides (1, 2). They include substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). In mice, SP and NKA are encoded by the gene Tac1, whereas NKB is encoded by the gene Tac2. These peptides act via three dis- tinct G-protein coupled receptors named neurokinin 1 (NK 1 ), NK 2 and NK 3 and encoded in the mouse by the genes Tacr1, Tacr2 and Tacr3, respectively. An established body of work has shown that tachykinins are able to influence the hypothalamic-pituitary-gonadal (HPG) axis (3, 4), with recent morphological and functional data in particular linking NKB to the reproductive axis. Rat studies suggest NKB-expressing neurones within the arcuate can influence luteinsing hormone (LH) secretion via projections to the axons of NK3R-expressing GnRH neurones in the median eminence (5). Central administration of Journal of Neuroendocrinology Correspondence to: Anthony P. Coll, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK (e-mail: apc36@cam.ac.uk). Growing evidence suggests the tachykinin neurokinin B (NKB) may modulate gonadotrophin secretion and play a role in sex-steroid feedback within the reproductive axis. NKB signalling has recently been identified as being necessary for normal human reproductive function, although the precise mechanisms underpinning this role remain to be established. We have used rodents to explore further the role of NKB within the reproductive axis. In particular, we have studied its interactions with kisspeptin, a neuropeptide essential for reproductive function in rodent and human with close anatomical links to NKB within the hypothalamus. Intraperitoneal administration of NKB (50 nmol) to male mice had no effect on circulating luteinsing hormone (LH) levels and, although i.p. kisspeptin (15 nmol) increased LH five-fold, co-administration of NKB and kisspeptin was indistinguishable from kisspeptin alone. Intracerebroventricular adminis- tration of NKB (10 nmol) to male mice also had no effect on LH levels, with 1 nmol kisspeptin i.c.v. significantly increasing LH compared to control (0.37 Æ 0.18 versus 5.11 Æ 0.28 ng ⁄ ml, respectively). Interestingly, i.c.v. co-administration of NKB and kisspeptin caused a significant increase in LH concentrations compared to kisspeptin alone (8.96 Æ 1.82 versus 5.11 Æ 0.28 ng ⁄ ml respectively). We used hypothalamic explants from rats to assess the effect of NKB on gonadotrpohin-releasing hormone (GnRH) secretion ex vivo. Doses of NKB up to 1000 nM failed to stimulate GnRH secretion, whereas 100 nM kisspeptin robustly increased GnRH secretion. Of note, co-administration of NKB with kisspeptin abrogated the effect of kisspeptin, producing no GnRH release above basal state. Finally, we analysed the expression of Tac2 ⁄ Tacr3 (genes encod- ing NKB and NK3R, respectively) within the arcuate nucleus in different nutritional states. After a 48-h fast, the expression of both Tac2 and Tacr3 showed a significant increase, in contrast to levels of Kiss1 and Kiss1r mRNA, which remained unchanged. In male rodent models, NKB and kisspeptin have different effects upon gonadotrophin release and appear to interact in a complex manner. Key words: NKB, kisspeptin, gonadotrophin, rodent. doi: 10.1111/j.1365-2826.2009.01951.x Journal of Neuroendocrinology 22, 181–187 ª 2010 The Authors. Journal Compilation ª 2010 Blackwell Publishing Ltd Journal of Neuroendocrinology From Molecular to Translational Neurobiology