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Kisspeptin signalling in the physiology and pathophysiology of the urogenital system

Nature Reviews Urology volume 13, pages 21–32 (2016)Cite this article

Subjects

Key Points

  • Kisspeptin — a peptide hormone that acts via the G-protein-coupled receptor KISS1R — is implicated in the regulation of a number of biological processes, such as reproduction, metabolism, and cancer metastasis

  • Kisspeptin–KISS1R signalling is involved in the physiology and pathophysiology of the urogenital system via both indirect (hypothalamic) and direct (gonadal) actions

  • Kisspeptin and KISS1R are expressed in the mammalian ovary and are responsive to various factors including gonadotropin, environmental, and metabolic cues

  • Kisspeptin expression in Leydig cells alters during different stages of postnatal developmental and is regulated by luteinizing hormone

  • Kisspeptin inhibits metastasis of various tumours, including urogenital carcinomas

Abstract

Kisspeptin is a peptide hormone, which signals via the G-protein-coupled kisspeptin receptor (KISS1R). Kisspeptin–KISS1R signalling has been implicated in various physiological and pathophysiological processes in the urogenital system, including critical roles in ovarian function as a key player in the regulation of oocyte development. Kisspeptin also has roles in several different functions of the male reproductive tract, such as spermatogenesis and sperm capacitation, and is also thought to be involved in kidney physiology — studies in preclinical animal models have reported that expression of kisspeptin and/or KISS1R is altered in chronically impaired kidneys. The wider importance of kisspeptin action in the urogenital tract has been highlighted by the finding that it suppresses metastasis of urogenital carcinomas; besides the possible therapeutic potential of this finding, tissue and tumour-stage-specific alterations in kisspeptin and KISS1/KISS1R expression could potentially be used as biomarkers for the diagnosis and prognosis of urogenital carcinomas.

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Figure 1: Possible mechanisms by which kisspeptins exert their biological actions via KISS1R.
Figure 2: Potential role of kisspeptin in the testis.
Figure 3: Potential role of kisspeptin in the ovary.
Figure 4: Effects of alterations in expression of kisspeptin peptide and/or the KISS1 and KISS1R genes on cellular processes leading to metastasis and tumour angiogenesis.

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Acknowledgements

F.W. is a Georg Forster Postdoctoral fellow of the Alexander von Humboldt Foundation, Germany. Funding for research work in R.B.'s laboratory is provided by the German Primate Center, which is a Leibniz Institute financed by the federal states and the Federal Republic of Germany. Research work in M.S.'s laboratory is supported by Higher Education Commission of Pakistan. The authors are thankful to Dr Stephanie Seminara, Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 0211, USA, for her comments on an earlier form of manuscript.

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Authors and Affiliations

  1. Stem Cell Biology Unit, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, D-37077, Göttingen, Germany

    Fazal Wahab & Rüdiger Behr

  2. Department of Developmental Biology, Faculty of Zoology and Anthropology, University of Göttingen, Justus-von-Liebig-Weg 11, 37077, Göttingen, Germany

    Bibi Atika

  3. Department of Animal Sciences, Laboratory of Reproductive Neuroendocrinology, Faculty of Biological Sciences, Quaid-i-Azam University, 45320, Islamabad, Pakistan

    Muhammad Shahab

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Wahab, F., Atika, B., Shahab, M. et al. Kisspeptin signalling in the physiology and pathophysiology of the urogenital system. Nat Rev Urol 13, 21–32 (2016). https://doi.org/10.1038/nrurol.2015.277

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