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Interactions Between Kisspeptins and Neurokinin B

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Kisspeptin Signaling in Reproductive Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 784))

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.

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Acknowledgments

This research was supported by the Marie Curie Outgoing International Fellowship within the seventh Framework Programme of the European Union. The author is grateful to Drs. Amy Oakley and Leonor Pinilla for their constructive comments on the manuscript and Drs. Manuel Tena-Sempere, Don Clifton, and Robert Steiner for their contribution to some of the studies highlighted in this chapter.

Conflict of interest: The author reports no conflicts of interest.

Disclosure: The author has nothing to disclose.

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  1. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Víctor M. Navarro Ph.D.

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  1. Víctor M. Navarro Ph.D.
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Correspondence to Víctor M. Navarro Ph.D. .

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  1. , Department of Reproductive Medicine, University of California, San Diego, La Jolla, 92093, California, USA

    Alexander S. Kauffman

  2. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Hackett Drive, Nedlands, 6009, West Australia, Australia

    Jeremy T. Smith

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Navarro, V.M. (2013). Interactions Between Kisspeptins and Neurokinin B. In: Kauffman, A., Smith, J. (eds) Kisspeptin Signaling in Reproductive Biology. Advances in Experimental Medicine and Biology, vol 784. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6199-9_15

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