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Research Article

性早熟雌性大鼠RFRP3 / GPR147的动态变化

卷 19, 期 10, 2019

页: [766 - 775] 页: 10

弟呕挨: 10.2174/1566524019666190906142445

open access plus

摘要

背景：青春期发育是受神经内分泌系统和下丘脑-垂体-性腺轴调节的复杂生理过程。性早熟是一种常见的儿童内分泌疾病。性早熟的发病机理尚未完全阐明。 RFRP3 / GPR147信号通路可能通过作用于GnRH神经元和垂体来调节促性腺激素的合成和释放，从而抑制禽类和哺乳动物的生殖能力。但是，关于RFRP3在青春期发育和性早熟中的作用知之甚少。目的：观察雌性大鼠模型下丘脑中RF酰胺相关肽3 / G蛋白偶联受体147（RFRP3 / GPR147）的动态变化，并探讨其在性早熟中的作用。 方法：将Sprague-Dawley雌性大鼠随机分为三组：正常，媒介物和性早熟模型。在5天大时，通过皮下注射达那唑溶解的乙醇和乙二醇的混合物来制备具有性早熟的大鼠模型。在不同的日龄（15、25、30、35和40天），通过酶检测外周血中雌二醇（E2），促卵泡激素（FSH）和黄体生成素（LH）的水平实时聚合酶链反应（RT PCR）检测免疫荧光法检测RFRP3的信使核糖核酸（mRNA），促性腺激素释放激素和GPR147的表达。使用免疫荧光共聚焦显微镜观察到RFRP3阳性细胞。 结果：在性早熟模型组中，在第25天和第30天，性激素水平和子宫系数显着高于正常组和媒介物组。性早熟模型大鼠的卵巢形态发育显着早于正常和媒介物组。在性早熟模型组中，RFRP3 / GPR147和GnRH的mRNA表达逐渐升高，并在25天达到峰值。不同日龄和交互作用对RFRP3 mRNA的表达具有统计学意义，而模型组和媒介物组的RFRP3 mRNA水平无统计学意义。模型组与媒介物组在不同日龄之间GPR147 mRNA的表达具有统计学意义。下丘脑RFRP3 / GPR147 mRNA和RFRP3阳性细胞的表达随着青春期的开始而逐渐降低。在35天时，性早熟模型组的RFRP3 mRNA和GPR147 mRNA的水平显着低于媒介物组。同时，性早熟模型大鼠的LH水平在该年龄达到峰值。在媒介物组中，RFRP3 mRNA水平和血清LH逐渐升高，并且LH在35日龄时几乎达到峰值。随后，它逐渐下降并达到35日龄的最低水平。 RFRP3 mRNA和LH的表达呈正相关。 结论：研究结果表明，RFRP3 / GPR147信号通路可能通过调节大鼠的青春期发育和性成熟而参与性早熟的发病机制。

关键词: 性早熟模型大鼠，RFamide相关肽3，G蛋白偶联受体147， 下丘脑-垂体-性腺轴。

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