Review of the Y chromosome, Sry and hypertension.

Review of the Y chromosome, Sry and hypertension.
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DOI:
10.1016/j.steroids.2009.10.015
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发表时间:
2010-11
期刊:
影响因子:
2.7
通讯作者:
Milsted, Amy
Milsted, Amy
中科院分区:
医学3区
文献类型:
--
作者:
Ely, Daniel;Underwood, Adam;Dunphy, Gail;Boehme, Shannon;Turner, Monte;Milsted, Amy

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下面的综述探讨了SHR Y染色体的作用,特别是Sry基因复合体在高血压和潜在的机制,涉及交感神经系统和肾素血管紧张素系统。在高血压方面存在一致的性别差异,在大多数哺乳动物种群中,男性受影响的比例高于女性。我们早期的研究表明,SHR大鼠血压(BP)的性别差异的一部分映射到SHR Y染色体。在大鼠中,具有SHR Y染色体的雄性比雌性或具有不同Y染色体的雄性具有更高的BP。与这些结果一致,一些人群研究证实了Y染色体对BP的影响。我们最近的研究集中在一个转录因子,Sry,作为位点不仅参与BP调制,但对其他表型的影响。Sry基因座是哺乳动物Y染色体上进化上保守的基因座,负责睾丸决定,并且是转录因子。Sry基因座含有负责DNA结合的高度保守的高迁移率族(HMG)盒区域。HMG盒中的突变导致性别逆转。我们在SHR和WKY雄性大鼠中发现了多个功能性Sry拷贝。有大量证据表明,睾丸决定可能不是Sry的唯一功能,因为它在成年男性的大脑,肾脏和肾上腺中表达。这些发现对涉及交感神经系统、肾素血管紧张素系统、雄激素受体调节和前列腺生理学的性别生理学研究具有潜在的意义。
The following review examines the role of the SHR Y chromosome and specifically the Sry gene complex in hypertension and potential mechanisms that involve the sympathetic nervous system and renin angiotensin system. There are consistent gender differences in hypertension, with a greater proportion of males affected than females in most mammalian populations. Our earlier studies demonstrated that a portion of the gender differences in blood pressure (BP) in the SHR rat mapped to the SHR Y chromosome. In rats, males with the SHR Y chromosome have higher BP than females, or males with a different Y chromosome. Consistent with these results, several human population studies have confirmed a Y chromosome effect on BP. Our more recent studies focus on a transcription factor, Sry, as the locus involved in not only BP modulation but effects on other phenotypes. The Sry locus is an evolutionarily conserved locus on the mammalian Y chromosome responsible for testis determination and is a transcription factor. The Sry locus contains a highly conserved High Mobility Group (HMG) box region responsible for DNA binding. Mutations in the HMG box result in sex reversal. We have found multiple functional copies of Sry in SHR and WKY male rats. There is abundant evidence that testes determination may not be Sry’s only function as it is expressed in the brain, kidney and adrenal gland of adult males. These findings have potential implications for gender physiology research which involve, the sympathetic nervous system, renin angiotensin system, androgen receptor regulation and prostate physiology.
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