Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary.
Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary.
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绵羊胎儿中枢神经系统和垂体中雄激素受体表达的个体发育。
DOI：
10.1016/j.neulet.2008.05.008
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发表时间：
2008
影响因子：
2.5
通讯作者：
Keller-Wood,Maureen
中科院分区：
文献类型：
--
作者：
Wood,CharlesE;Keller-Wood,Maureen
在胎羊中，循环雄激素影响胎儿应激反应和分娩时间。然而，很少有人知道雄激素受体（AR）在胎儿大脑中的存在和发展。本研究旨在验证雄激素受体在胎儿大脑和垂体中表达以及AR丰度受个体遗传学调节的假设。我们从妊娠80、100、120、130和145天以及出生后1和7天的胎羊的垂体、下丘脑、海马和脑干中分离mRNA（每组n=4-5）。使用实时RT-PCR，我们测量了这些脑区和垂体中受体的mRNA表达水平。在另一项研究中，我们从80（n=3），120（n=4）和145（n=4）天的胎羊相同脑区分离蛋白质。下丘脑AR mRNA表达在孕晚期增加，从145天开始，出生后进行性增加。下丘脑中AR蛋白的增加趋势不明显。孕80 d后垂体AR mRNA表达升高，孕晚期不再升高或降低，孕晚期AR蛋白表达显著升高。在海马和脑干中，AR mRNA在整个妊娠后半期是恒定的，并且AR蛋白低于我们的Western印迹分析的灵敏度。我们的结论是，胎儿大脑和垂体的循环雄激素或雄激素前体在胎儿血浆中的目标网站，我们推测，在下丘脑的雄激素的行动增加，出生前立即可能是不可或缺的分娩时间。
In fetal sheep, circulating androgens influence fetal stress responsiveness and the timing of parturition. Nevertheless, little is known about the presence and development of androgen receptors (ARs) in the fetal brain. The present study was undertaken to test the hypothesis that expression of androgen receptor occurs in fetal brain and pituitary, and that the abundance of the AR is ontogenetically regulated. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, and 145-day gestation, and 1 and 7 days postnatal (n=4–5 per group). Using real-time RT-PCR, we measured mRNA expression levels of the receptor in these brain regions and pituitary. In a separate study, we isolated protein from the same brain regions in fetal sheep that were 80 (n=3), 120 (n=4), and 145 (n=4) days. AR mRNA expression in hypothalamus increased in late gestation, starting at 145 days, and increasing progressively after birth. A trend of increasing AR protein in hypothalamus was not significant. AR mRNA expression in pituitary was elevated after 80 days gestation, but with no further increases or decreases in late gestation, while AR protein increased significantly at the end of gestation. In hippocampus and brainstem AR mRNA was constant throughout the latter half of gestation, and AR protein was below the sensitivity of our Western blot assay. We conclude that the fetal brain and pituitary are target sites for circulating androgens or androgen precursors in fetal plasma, and we speculate that the increase in hypothalamic action of androgens immediately prior to birth might be integral to the timing of parturition.