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Kisspeptin Signaling in Reproductive Biology pp 133–158Cite as

Molecular Biology of the Kisspeptin Receptor: Signaling, Function, and Mutations

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

Abstract

Kisspeptin receptor (KISS1R) signaling is essential for the hallmark increase in pulsatile GnRH secretion characteristic of the onset of puberty in humans and experimental animals. Loss-of-function mutations in KISS1R are associated with idiopathic hypogonadotropic hypogonadism in humans. Also, mutations with confirmed association with idiopathic central precocious puberty were identified in kisspeptin and KISS1R. These observations underscore the role of KISS1R signaling for normal pubertal development. Moreover, investigation of the mechanisms underlying the gain-of-function mutation in KISS1R indicates that the duration of KISS1R signaling is critical for the role of this receptor in timing the onset of puberty in humans. These findings further endorse the need to uncover the mechanisms, as well as yet-unknown proteins, involved in each step of KISS1R signaling. This knowledge is expected to advance our understanding of normal and abnormal pubertal development, as well as to help uncover the role of KISS1R signaling in non-hypothalamic tissues such as the placenta. This chapter discusses recent advances in the investigation of KISS1R signaling and function, as well as potential pathophysiological implications of naturally occurring mutations in this receptor identified in humans with reproductive disorders.

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Acknowledgments

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), through cooperative agreement U54 HD28138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, by R01 HD61577, and by R21 HD66495 (to UBK) as well as by the R21 HD059015 and ARRA R21 HD059015-02S1 (SDCB) and by the 2008 Child Health Research Award from the Charles H. Hood Foundation, Boston, MA (SDCB).

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Authors and Affiliations

  1. Department of Molecular and Cellular Pharmacology and Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA

    Suzy Drummond Carvalho Bianco

  2. Division of Endocrinology, Department of Medicine, Harvard Medical School/Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA

    Ursula B. Kaiser M.D.

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  1. Suzy Drummond Carvalho Bianco
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Correspondence to Ursula B. Kaiser M.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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Bianco, S.D.C., Kaiser, U.B. (2013). Molecular Biology of the Kisspeptin Receptor: Signaling, Function, and Mutations. 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_7

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