title: Expression and actions of GnIH and its orthologs in vertebrates: Current status and advanced knowledge.
abstract: The physiology of reproduction is very complex and is regulated by multiple factors, including a number of hypothalamic neuropeptides. In last few decades, various neuropeptides have been discovered to be involved in stimulation or inhibition of reproduction. In 2000, Tsutsui and colleagues uncovered gonadotropin-inhibitory hormone (GnIH), a neuropeptide generating inhibitory drive to the reproductive axis, in the brain of Coturnix quail. Afterward, GnIH orthologs were discovered in other vertebrates from fish to mammals including human. In these vertebrates, all the discovered GnIH and its ortholgs have LPXRFamide (X=L or Q) sequence at C-terminus. GnIH orthologs of mammals and primates are also termed as RFamide-related peptide (RFRP)-1 and -3 that too have an LPXRFamide (X=L or Q) motif at their C-terminus. GnIH and its orthologs form a member of the RFamide peptide family. GnIH signals via its canonical G protein coupled receptor 147 (GPR147). Both GnIH and GPR147 are expressed in hypothalamus and other brain regions. Besides actions through the hypothalamic GnRH and kisspeptinergic neurons, GnIH-GPR147 signaling exerts inhibitory effect on the reproductive axis via pituitary gonadotropes and directly at gonadal level. Various factors including availability and quality of food, photoperiod, temperature, social interaction, various stresses and some diseases modulate GnIH-GPR147 signaling. In this review, we have discussed expression and actions of GnIH and its orthologs in vertebrates. Special emphasis is given on the role of GnIH-GPR147 signaling pathway in the regulation of reproduction. We have also reviewed and discussed currently available literature on the participation of GnIH-GPR147 signaling pathway in the stress modulation of reproduction.
authors.affiliation: Department of Endocrinology, Children Hospital of Zhejiang University, School of Medicine, Zhejiang University, Hangzhou, China; Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Key Laboratory of Medical Neurobiology of Ministry of Health and Zhejiang Province, Department of Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Rahim
authors.initials: R
authors.lastname: Ullah
authors.affiliation: Key Laboratory of Medical Neurobiology of Ministry of Health and Zhejiang Province, Department of Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Key Laboratory of Medical Neurobiology of Ministry of Health and Zhejiang Province, Department of Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Zhou
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Children Hospital of Zhejiang University, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: fjf68@qq.com.
authors.forename: Jun-Fen
authors.initials: JF
authors.lastname: Fu
authors.affiliation: Stem Cell Biology Unit, German Primate Center, Leibniz-Institute for Primate Research, Kellnerweg 4, 37077 Gottingen, Germany.
authors.forename: Fazal
authors.initials: F
authors.lastname: Wahab
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: shahab@qau.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahab
mesh_terms: D000818:Animals; D003370:Coturnix; D005260:Female; D006801:Humans; D007028:Hypothalamic Hormones / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007028:Hypothalamic Hormones; D009479:Neuropeptides; C416987:RFamide peptide
keywords: GnIH; GnIH orthologs; Neuroendocrinology; Photoperiod; Reproduction; Stress