title: Glucocorticoid receptor-mediated regulation of Rfrp (GnIH) and Gpr147 (GnIH-R) synthesis in immortalized hypothalamic neurons.
abstract: A novel RFamide peptide, gonadotropin-inhibitory hormone (GnIH) has emerged as a modulator of avian reproduction. However, the functional role of the mammalian homologue, RFRP-3 remains poorly understood. The RFRP-3 neuronal circuit is influenced by the stress axis. However, whether the Rfrp gene is under direct glucocorticoid (GC)-mediated transcriptional regulation, in the presence and absence of the gonadal steroid, 17β-estradiol, is unknown. We investigated the regulation of the Rfrp (GnIH) and Gpr147 (GnIH-R) transcripts by steroids in a novel hypothalamic Rfrp-expressing cell model, rHypoE-23. The GC agonist, dexamethasone increased Rfrp and Gpr147 mRNA levels. Dexamethasone acted directly on the nuclear GC receptor (GR) to mediate GC-dependent transcriptional changes, independently of de novo protein synthesis. 17β-estradiol had no significant effect on Rfrp or Gpr147 biosynthesis in these neurons. This suggests that Rfrp-expressing neurons serve as potential upstream mediators of stress-induced effects through GR-dependent mechanisms.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Gojska
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Departments of Medicine and Obstetrics and Gynaecology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5S 1A8, Canada. Electronic address: d.belsham@utoronto.ca.
authors.forename: Denise D
authors.initials: DD
authors.lastname: Belsham
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D007028:Hypothalamic Hormones / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D005938:Glucocorticoids; D007028:Hypothalamic Hormones; C000588859:RFamide-related peptide-3, rat; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D004958:Estradiol; D003907:Dexamethasone
keywords: GPR147; Glucocorticoids; GnIH; Hypothalamus; RFamide-related peptide; Stress