Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in females and maturation in young adults. Reproductive function is highly dependent on levels of both neurokinin B and also the G-protein coupled receptor ligand kisspeptin. The first NKB studies done attempted to resolve why high levels of the peptide may be implicated in pre-eclampsia during pregnancy. NKB, kisspeptin, and dynorphin together are found in the arcuate nucleus (ARC) known as the KNDy subpopulation. This subpopulation is targeted by many steroid hormones and works to form a network that feeds back to GnRH pulse generator. Synthesis Neurokinin B is found in humans as a ten-peptide chain (decapeptide) attached to a terminal amide group. The peptide formula is H-Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2 (DMHDFFVGLM-NH2). Neurokinin B (NKB), is encoded by the TAC3 gene in humans and Tac2 in rodent species. Neurokinin B is expressed along with the peptides kisspeptin and dynorphin A in the neuronal cells of the arcuate nucleus. Five exon segments in the TAC3 gene encode for the NKB precursor known as preprotachykinin B. Preprotachykinin B is then proteolytically cleaved into the pro-peptide proneurokinin B. A second proteolytic cleavage of proneurokinin B produces the final product neurokinin B. Role in humans During the ovarian cycle, GnRH secretion along with that of luteinizing hormone (LH) is highly regulated. This regulation occurs by a negative feedback system. Neurokinin B along with its sister peptides of the KNDy subpopulation regulate this feedback. The NK3R receptor group when activated with a synthetic agonist of NKB, senktide, has been shown to stimulate the secretion of luteinizing hormone. In addition, studies have shown that NKB plays a larger role in females than in males. It has been found that in brain of females, the arcuate nucleus contains twice as many connections to NKB neurons than males. Receptors The main receptor neurokinin B interacts with is the neurokinin 3 receptor (NK3R). The Neurokinin 3 receptor is a part of a larger family of G-protein coupled receptors that binds all tachykinin proteins. While neurokinin B has the ability to bind to other Neurokinin receptors, the highest affinity lies in that of the NK3R receptor group. Much like the neurokinin B peptide, the NK3R receptor that it binds to is encoded within five exons of the TACR3