Evolutionally Conserved Function of Kisspeptin Neuronal System Is Nonreproductive Regulation as Revealed by Nonmammalian Study

  • Mikoto Nakajo
    Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
  • Shinji Kanda
    Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
  • Tomomi Karigo
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California
  • Akiko Takahashi
    Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
  • Yasuhisa Akazome
    Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan
  • Yoshihisa Uenoyama
    Graduate School of Bioagricultural Sciences, Nagoya University, Aichi Japan
  • Makito Kobayashi
    Department of Life Science, International Christian University, Tokyo, Japan
  • Yoshitaka Oka
    Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan

書誌事項

公開日
2017-10-18
資源種別
journal article
DOI
  • 10.1210/en.2017-00808
公開者
The Endocrine Society

説明

The kisspeptin neuronal system, which consists of a neuropeptide kisspeptin and its receptor Gpr54, is considered in mammals a key factor of reproductive regulation, the so-called hypothalamic-pituitary-gonadal (HPG) axis. However, in nonmammalian vertebrates, especially in teleosts, existence of kisspeptin regulation on the HPG axis is still controversial. In this study, we applied multidisciplinary techniques to a teleost fish, medaka, and examined possible kisspeptin regulation on the HPG axis. First, we generated knockout medaka for kisspeptin-related genes and found that they show normal fertility, gonadal maturation, and expression of gonadotropins. Moreover, the firing activity of GnRH1 neurons recorded by the patch clamp technique was not altered by kisspeptin application. Furthermore, in goldfish, in vivo kisspeptin administration did not show any positive effect on HPG axis regulation. However, as kisspeptin genes are completely conserved among vertebrates except birds, we surmised that kisspeptin should have some important nonreproductive functions in vertebrates. Therefore, to discover novel functions of kisspeptin, we generated a gpr54-1:enhanced green fluorescent protein (EGFP) transgenic medaka, whose gpr54-1-expressing cells are specifically labeled by EGFP. Analysis of neuronal projection of gpr54-1:EGFP-expressing neurons showed that these neurons in the ventrolateral preoptic area project to the pituitary and are probably involved in endocrine regulation other than gonadotropin release. Furthermore, combination of deep sequencing, histological, and electrophysiological analyses revealed various novel neural systems that are under control of kisspeptin neurons-that is, those expressing neuropeptide Yb, cholecystokinin, isotocin, vasotocin, and neuropeptide B. Thus, our new strategy to genetically label receptor-expressing neurons gives insights into various kisspeptin-dependent neuronal systems that may be conserved in vertebrates.

収録刊行物

  • Endocrinology

    Endocrinology 159 (1), 163-183, 2017-10-18

    The Endocrine Society

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