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Direct Regulation of Gonadotrophin‐Releasing Hormone (GnRH) Transcription By RF‐Amide‐Related Peptide‐3 and Kisspeptin in A Novel GnRH‐Secreting Cell Line, mHypoA‐GnRH/GFP
Author(s) -
Gojska N. M.,
Friedman Z.,
Belsham D. D.
Publication year - 2014
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12225
Subject(s) - kisspeptin , medicine , endocrinology , gonadotropin releasing hormone , messenger rna , hypothalamus , receptor , biology , hormone , chemistry , luteinizing hormone , gene , biochemistry
RF‐amide‐related peptide‐3 [RFRP‐3; also often referred to as the mammalian orthologue of the avian gonadotrophin‐inhibitory hormone (GnIH)] and kisspeptin have emerged as potent modulators of neuroendocrine function via direct regulation of the reproductive axis in the hypothalamus and pituitary. There are few studies focusing on the direct regulatory effects of RFRP‐3 and kisspeptin on gonadotrophin‐releasing hormones (GnRH) neurones. We report their effect on GnRH mRNA expression and release in a novel GnRH neuronal cell model, mH ypoA‐GnRH/GFP, generated from adult‐derived GnRH‐GFP neurones. The neurones express receptors for both RFRP‐3 and kisspeptin, Gpr147 and Gpr54, respectively. Incubation with 100 n m RFRP‐3 results in attenuation of GnRH mRNA expression by approximately 60%. Conversely, incubation with 10 n m of Kiss‐10 induced GnRH mRNA expression, whereas the combined effect was an overall repression of GnRH mRNA levels. With transcription inhibitors, the repression of GnRH mRNA levels was linked to a transcriptional mechanism but not mRNA stability. No significant changes in GnRH secretion were observed upon RFRP‐3 exposure in these neurones. Our findings suggest that the suppressive signalling of RFRP‐3 on GnRH transcription may dominate over kisspeptin induction in the mH ypoA‐GnRH/GFP GnRH neuronal cell model.