Estradiol control of expression and levels of estradiol-binding proteins in the medial preoptic area, medial hypothalamus and pituitary

Estradiol control of expression and levels of estradiol-binding proteins in the medial preoptic area, medial hypothalamus and pituitary
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DOI:
10.1159/000071961
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发表时间:
2003-08-01
期刊:
影响因子:
4.1
通讯作者:
Caldwell, JD
Caldwell, JD
中科院分区:
医学2区
文献类型:
--
作者:
Gao, G;Herbert, Z;Caldwell, JD

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哺乳动物的大脑中至少有三种雌二醇结合蛋白:雌二醇受体α (erα)、erβ和性激素结合球蛋白(SHBG)。在本研究中,我们使用逆转录聚合酶链反应(RT-PCR)比较了雌二醇处理对去卵巢大鼠两个生殖重要脑区,内侧视前区-下丘脑前部(MPOA-AH)和内侧下丘脑(MH)以及海马中这三种雌二醇结合蛋白mRNA表达的影响。我们还采用表面增强激光解吸电离飞行时间(SELDI-TOF)质谱法(MS)分析雌二醇对去卵巢大鼠MPOA-MH和神经垂体SHBG水平的影响。去卵巢大鼠体内雌二醇处理消除或显著降低了MPOA-AH和MH中所有三种雌二醇结合蛋白的表达。海马中没有发生erα、erβ和SHBG表达的变化。Northern blot和DNA序列分析证实了RT-PCR对SHBG的检测结果。SELDI-TOF质谱分析表明,体内雌二醇处理导致下丘脑SHBG水平显著降低,并且通过雌二醇处理降低SHBG mRNA也导致SHBG蛋白水平降低。雌二醇治疗也消除了神经垂体中可检测到的SHBG,表明雌二醇控制了该释放部位的SHBG水平。体内雌二醇处理对SHBG和两种er的mRNA水平具有相同的抑制作用,这表明大脑中所有三种类固醇结合蛋白的翻译控制机制相似。雌二醇治疗也降低了垂体SHBG,这表明这种治疗从神经垂体释放SHBG。版权所有(C) 2003 S. Karger AG,巴塞尔。
The brains of mammals have at least three estradiol-binding proteins: estradiol receptor-alpha (ERalpha), ERbeta, and sex hormone-binding globulin (SHBG). In this study we compare the effects of estradiol treatment on the expression of mRNA for these three estradiol-binding proteins in two reproductively important brain areas, the medial preoptic area-anterior hypothalamus (MPOA-AH) and medial hypothalamus (MH) as well as in the hippocampus in ovariectomized rats, using the reverse transcriptase-polymerase chain reaction (RT-PCR). We also used surface-enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry (MS) to analyze the effects of estradiol in ovariectomized rats on SHBG levels in the MPOA-MH as well as the neurohypophysis. In vivo estradiol treatment in ovariectomized rats eliminated or significantly reduced expression of all three estradiol-binding proteins in both the MPOA-AH and MH. This change in ERalpha, ERbeta, and SHBG expression did not occur in the hippocampus. Both Northern blot and DNA sequence analysis confirmed the results of the RT-PCR for SHBG. SELDI-TOF MS analysis demonstrated that in vivo estradiol treatments resulted in dramatically decreased levels of SHBG in the hypothalamus and that a reduction in SHBG mRNA by estradiol treatment also resulted in a reduction in SHBG protein levels. Estradiol treatment also eliminated detectable SHBG from the neurohypophysis, suggesting that estradiol controls SHBG levels in this release site. That in vivo estradiol treatments had the same inhibitory effects on mRNA levels for SHBG and both ERs suggests similar translational control mechanisms for all three steroid-binding proteins in the brain. That estradiol treatments also reduced pituitary SHBG suggests that such treatment releases SHBG from the neurohypophysis. Copyright (C) 2003 S. Karger AG, Basel.