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

Nakajo, Mikoto and Kanda, Shinji and Karigo, Tomomi and Takahashi, Akiko and Akazome, Yasuhisa and Uenoyama, Yoshihisa and Kobayashi, Makito and Okamoto, Yoshitaka (2018) Evolutionally Conserved Function of Kisspeptin Neuronal System Is Nonreproductive Regulation as Revealed by Nonmammalian Study. Endocrinology, 159 (1). pp. 163-183. ISSN 0013-7227. http://resolver.caltech.edu/CaltechAUTHORS:20171030-132156693

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1210/en.2017-00808DOIArticle
https://academic.oup.com/endo/article/doi/10.1210/en.2017-00808/4555284PublisherArticle
Additional Information:© 2018 Endocrine Society. Received: 01 September 2017; Accepted: 10 October 2017; Published: 18 October 2017. We thank Dr. Shinya Oishi (Kyoto University) for helpful advice and presenting FTM145, and Dr. Kataaki Okubo (University of Tokyo) and Dr. Towako Kajiyama-Hiraki (RIKEN) for helpful advice and gifts of constructs for npb ISH probes. We also thank Dr. Toyoji Kaneko (University of Tokyo) for helpful advice and for providing the equipment for keeping goldfish. We are grateful to Dr. Buntaro Zempo (Osaka Medical College) for helpful suggestions in ISH protocols. We also thank Martin J. Kelly, Oline K. Rønnekleiv, and Martha Bosch (Oregon Health and Science University) for helpful advice for the cell harvesting procedure for deep sequencing, and Miho Kyokuwa and Hisako Kohno for daily care of the fish used in this study. Thanks are also due to Dr. Takeshi Kaneko (Kyoto University) and Dr. Hiroyuki Hioki (Kyoto University) for providing the anti-EGFP antibody, and to Dr. Hiroshi Hosokawa (Kyoto University) for help in establishing the behavior assays. The RIA was performed at the Nagoya University Radioisotope Center. This work was supported by Grants-in-Aid from Japan Society for the Promotion of Science Grants 15J06435 (to M.N.) and 26840111, a Suntory Foundation for Life Sciences grant (SUNBOR; to S.K.), and Japan Society for the Promotion of Science Grant 26221104, as well as by the Program for Promotion of Basic Research Activities for Innovative Biosciences of Japan (to Y.O.). This work was also supported by Graduate Program for Leaders in Life Innovation (GPLLI), the University of Tokyo Life Innovation Leading Graduate School from MEXT, Japan. The authors have nothing to disclose.
Funders:
Funding AgencyGrant Number
Japan Society for the Promotion of Science (JSPS)15J06435
Japan Society for the Promotion of Science (JSPS)26840111
Suntory Foundation for Life SciencesUNSPECIFIED
Japan Society for the Promotion of Science (JSPS)26221104
Program for Promotion of Basic Research Activities for Innovative Biosciences of JapanUNSPECIFIED
Ministry of Education, Culture, Sports, Science and Technology (MEXT)UNSPECIFIED
Record Number:CaltechAUTHORS:20171030-132156693
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20171030-132156693
Official Citation:Mikoto Nakajo, Shinji Kanda, Tomomi Karigo, Akiko Takahashi, Yasuhisa Akazome, Yoshihisa Uenoyama, Makito Kobayashi, Yoshitaka Oka; Evolutionally Conserved Function of Kisspeptin Neuronal System Is Nonreproductive Regulation as Revealed by Nonmammalian Study, Endocrinology, Volume 159, Issue 1, 1 January 2018, Pages 163–183, https://doi.org/10.1210/en.2017-00808
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:82772
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Oct 2017 20:34
Last Modified:05 Feb 2018 20:57

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