Gojska Nicole M, Belsham Denise D
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
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.
Mol Cell Endocrinol. 2014 Mar 25;384(1-2):23-31. doi: 10.1016/j.mce.2013.12.015. Epub 2014 Jan 8.
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.
一种新型的RFamide肽，促性腺激素抑制激素（GnIH）已成为禽类繁殖的调节剂。然而，哺乳动物同源物RFRP-3的功能作用仍知之甚少。RFRP-3神经元回路受应激轴影响。然而，在存在和不存在性腺类固醇17β-雌二醇的情况下，Rfrp基因是否受直接糖皮质激素（GC）介导的转录调控尚不清楚。我们在一种新型的下丘脑表达Rfrp的细胞模型rHypoE-23中研究了类固醇对Rfrp（GnIH）和Gpr147（GnIH-R）转录本的调控。GC激动剂地塞米松增加了Rfrp和Gpr147的mRNA水平。地塞米松直接作用于核GC受体（GR），以介导GC依赖性转录变化，与从头蛋白质合成无关。17β-雌二醇对这些神经元中的Rfrp或Gpr147生物合成没有显著影响。这表明表达Rfrp的神经元通过GR依赖性机制作为应激诱导效应的潜在上游介质。
