Centre for Neuroendocrinology and Departments of Anatomy and Structural Biology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
J Neuroendocrinol. 2010 Apr;22(4):309-16. doi: 10.1111/j.1365-2826.2010.01963.x. Epub 2009 Jan 27.
RFamide related peptides (RFRPs) have been extensively implicated in the neuroendocrine control of reproduction. While steroid hormones strongly regulate the closely-related kisspeptin gene and protein expression, the regulation of RFRPs or their receptor by steroid hormones is almost unknown. The present study aimed to quantify relative levels of RFRP and Kiss1 gene expression and their G protein-coupled receptors (GPR147 and GPR54, respectively) in various brain areas and the pituitary gland, and to determine the effects of differing levels of oestradiol and pubertal development on levels of these gene products. In Experiment 1, the treatment groups examined were: dioestrus, ovariectomised and ovariectomised with replacement oestradiol to induce a preovulatory-like luteinising hormone surge. Micropunched brain regions and whole pituitary glands were processed for measurement of RFRP, Kiss1, GPR147 and GPR54 mRNA by quantitative reverse transcriptase-polymerase chain reaction. As expected, Kiss1 gene expression was low in the rostral periventricular area of the third ventricle of ovariectomised animals, whereas levels were highest in the arcuate nucleus in this situation. No such oestrogenic effects were observed for RFRP gene expression. GPR147 gene expression was highest in the rostral periventricular region of the third ventricle. The levels of GPR147 and GPR54 mRNA were markedly lower in the pituitary gland than in the hypothalamic regions, and RFRP and Kiss1 mRNA were virtually undetectable in the pituitary gland. These data imply that the actions of RFamides are likely to be predominantly central in nature. In Experiment 2, hypothalamic RFRP and GPR147 mRNA levels were measured in male and female rats aged 2, 4, 6 and 8 weeks. In females, RFRP gene expression increased with developmental age, peaking around the time of puberty, whereas in males gene expression increased between 2 and 4 weeks of age. These results suggest a role in the regulation of adult reproduction rather that prepubertal infertility.
RFamide 相关肽 (RFRP) 在生殖的神经内分泌控制中被广泛涉及。虽然类固醇激素强烈调节密切相关的 kisspeptin 基因和蛋白质表达，但类固醇激素对 RFRP 或其受体的调节几乎未知。本研究旨在定量测量不同脑区和垂体中 RFRP 和 Kiss1 基因表达及其 G 蛋白偶联受体 (GPR147 和 GPR54) 的相对水平，并确定不同水平的雌激素和青春期发育对这些基因产物水平的影响。在实验 1 中，检查的处理组为：发情期、卵巢切除和卵巢切除并用雌激素替代以诱导类似排卵的促黄体生成素激增。用定量逆转录聚合酶链反应测量微穿孔脑区和整个垂体中的 RFRP、Kiss1、GPR147 和 GPR54 mRNA。正如预期的那样，在卵巢切除动物的第三脑室前室周区，Kiss1 基因表达水平较低，而在这种情况下，水平最高的是弓状核。RFRP 基因表达没有观察到这种雌激素作用。GPR147 基因表达在第三脑室前室周区最高。GPR147 和 GPR54 mRNA 的水平在垂体中明显低于下丘脑区域，并且 RFRP 和 Kiss1 mRNA 在垂体中几乎无法检测到。这些数据表明，RFamides 的作用可能主要是中枢性的。在实验 2 中，测量了 2、4、6 和 8 周龄雄性和雌性大鼠下丘脑的 RFRP 和 GPR147 mRNA 水平。在雌性中，RFRP 基因表达随发育年龄增加，在青春期时达到峰值，而在雄性中，基因表达在 2 至 4 周龄之间增加。这些结果表明，它在调节成年生殖中起作用，而不是青春期不孕。
