title: Interactions between kisspeptins and neurokinin B.
abstract: Reproductive function is tightly regulated by an intricate network of central and peripheral factors; however, the precise mechanism triggering critical reproductive events, such as puberty onset, remains largely unknown. Recently, the neuropeptides kisspeptin (encoded by Kiss1) and neurokinin B (NKB, encoded by TAC3 in humans and Tac2 in rodents) have been placed as essential gatekeepers of puberty. Studies in humans and rodents have revealed that loss-of-function mutations in the genes encoding either kisspeptin and NKB or their receptors, Kiss1r and neurokinin 3 receptor (NK3R), lead to impaired sexual maturation and infertility. Kisspeptin, NKB, and dynorphin A are co-expressed in neurons of the arcuate nucleus (ARC), so-called Kisspeptin/NKB/Dyn (KNDy) neurons. Importantly, these neurons also co-express NK3R. Compelling evidence suggests a stimulatory role of NKB (or the NK3R agonist, senktide) on LH release in a number of species. This effect is likely mediated by autosynaptic inputs of NKB on KNDy neurons to induce the secretion of gonadotropin-releasing hormone (GnRH) in a kisspeptin--dependent manner, with the coordinated actions of other neuroendocrine factors, such as dynorphin, glutamate, or GABA. Thus, we have proposed a model in which NKB feeds back to the KNDy neuron to shape the pulsatile release of kisspeptin, and hence GnRH, in a mechanism also dependent on the sex steroid level. Additionally, NKB may contribute to the regulation of the reproductive function by metabolic cues. Investigating how NKB and kisspeptin interact to regulate the gonadotropic axis will offer new insights into the control of GnRH release during puberty onset and the maintenance of the reproductive function in adulthood, offering a platform for the understanding and treatment of a number of reproductive disorders.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA. vnavarro@partners.org
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Navarro
mesh_terms: D000818:Animals; D004399:Dynorphins; D018698:Glutamic Acid / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D009154:Mutation; D015287:Neurokinin B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011627:Puberty / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D018042:Receptors, Neurokinin-3 / Q000235:genetics / Q000378:metabolism; D012377:Rodentia; D012741:Sexual Maturation / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; D015287:Neurokinin B; D007986:Luteinizing Hormone
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