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Direct Steroidal Regulation and Inhibitory Mode of Action of Gonadotropin-inhibitory Hormone (GnIH or RFRP-3) in Immortalized Hypothalamic Cell Models

Fertility is dependent on the precisely orchestrated communication of an array of effectors within the reproductive axis, all of which impinge on gonadotropin-releasing hormone (GnRH) neurons. A novel reproductive inhibitor was identified in avian species and growing evidence suggests that the functional mammalian homologue, RFamide-related peptide-3 (RFRP-3 or GnIH) can inhibit GnRH neuronal activity and gonadotropin release. To date, the regulation and effects of RFRP-3 at the hypothalamic level are poorly understood. We established an Rfrp-expressing neuronal cell model to investigate the mechanisms of transcriptional regulation of the genes for RFRP and the RFRP receptor, GPR147 by dexamethasone and estradiol. We show that the RFRP system is a direct target for stress-associated transcriptional regulation. Further, employing a novel GnRH-secreting cell line, we report that GnRH neurons express Gpr147 and RFRP-3 represses the transcription of GnRH. These data further our understanding of the level and regulatory effects at which RFRP-3 modulates reproduction.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65437
Date18 June 2014
CreatorsGojska, Nicole
ContributorsBelsham, Denise D.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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