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Front. Endocrinol. | doi: 10.3389/fendo.2019.00110

Molecular Mechanisms of Gonadotropin-Inhibitory Hormone (GnIH) Actions in Target Cells and Regulation of GnIH Expression

  • 1Department of Ophthalmology, School of Medicine, Keio University, Japan
  • 2Department of Biology, Waseda University, Japan

Since gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as the first hypothalamic neuropeptide that actively inhibits gonadotropin release, researches conducted for the last 18 years have demonstrated that GnIH acts as a pronounced negative regulator of reproduction. Inhibitory effect of GnIH on reproduction is mainly accomplished at hypothalamic-pituitary levels; gonadotropin-releasing hormone (GnRH) neurons and gonadotropes are major targets of GnIH action based on the morphological interaction with GnIH neuronal fibers and the distribution of GnIH receptor. Here, we review molecular studies mainly focusing on the signal transduction pathway of GnIH in target cells, GnRH neurons and gonadotropes. The use of well-defined cellular model systems allows the mechanistic study of signaling pathway occurring in target cells by demonstrating the direct cause-and-effect relationship. The insights gained through studying molecular mechanism of GnIH action contribute to deeper understanding of the mechanism of how GnIH communicates with other neuronal signaling systems to control our reproductive function. Reproductive axis closely interacts with other endocrine systems, thus GnIH expression levels would be changed by adrenal and thyroid status. We also briefly review molecular studies investigating the regulatory mechanisms of GnIH expression to understand the role of GnIH as a mediator between adrenal, thyroid and gonadal axes.

Keywords: gonadotropin-inhibitory hormone/RFamide-related peptides (GnIH/RFRPs), GnIH receptor (GnIH-R), Gonadotropin-releasing hormone (GnRH), Kisspeptin, Vasoactive intestinal polypeptide (VIP), gonadotropes, Glucocorticoid (GC), Thyroid hormone (TH)

Received: 22 Nov 2018; Accepted: 06 Feb 2019.

Edited by:

Honoo Satake, Suntory Foundation for Life Sciences, Japan

Reviewed by:

Valerie Simonneaux, Centre National de la Recherche Scientifique (CNRS), France
Kataaki Okubo, The University of Tokyo, Japan  

Copyright: © 2019 Son, Ubuka and Tsutsui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. You Lee Son, School of Medicine, Keio University, Department of Ophthalmology, Tokyo, Japan, youleeson@keio.jp