The human testis-determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism.
The human testis-determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism.
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DOI：
10.1111/j.1471-4159.2012.07782.x
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发表时间：
2012-07
影响因子：
4.7
通讯作者：
Harley VR
中科院分区：
文献类型：
--
作者：
Czech DP;Lee J;Sim H;Parish CL;Vilain E;Harley VR
男性性别是由Y染色体上的性别决定区（SRY）转录因子决定的。SRY在控制雄性啮齿动物自主运动中的意外作用表明它在调节多巴胺传递和多巴胺相关的性别偏见疾病（如帕金森病）中的作用。我们在体外研究了SRY在人脑中的表达及其功能。在酪氨酸羟化酶（TH）阳性神经元亚群中的黑质致密部（SNc）中检测到SRY免疫反应性，而在女性中未检测到。SRY蛋白还与腹侧被盖区TH阳性神经元和网状黑质（SNr）中gad阳性神经元共定位。视黄酸诱导前体细胞NT2向多巴胺能细胞（NT2N）分化，使TH、NURR1、D2R和SRY表达增加。在人神经母细胞瘤细胞系M17中，SRY敲低导致TH、DDC、DBH和MAO-A表达降低；控制多巴胺合成和代谢的酶。相反，SRY过表达使TH、DDC、DBH、D2R和MAO-A水平升高，同时胞外多巴胺水平升高。荧光素酶分析表明，SRY激活了人类TH启动子/黑素增强子的4.6 kb 5 '上游调控区域。综上所述，这些结果表明SRY可能在人类男性中脑中发挥儿茶酚胺合成和代谢的积极调节作用。鉴于人体组织分析的局限性，需要进一步的研究来提供SRY在人脑区域表达的明确答案。
The male sex is determined by the sex determining region on the Y chromosome (SRY) transcription factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in regulation of dopamine transmission and dopamine-related disorders with sex bias such as Parkinson’s disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female, substantia nigra pars compacta (SNc) within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localised with TH positive neurons in the ventral tegmental area and GAD-positive neurons in the substantia nigra pars reticulate (SNr). Retinoic acid-induced differentiation of precursor NT2 cells into dopaminergic cells (NT2N) increased expression of TH, NURR1, D2R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY overexpression increased TH, DDC, DBH, D2R and MAO-A levels, which was accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5′ upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY may play a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. Given the limitations of human tissue analysis, further studies are required to provide a definitive answer on SRY expression in human brain regions.
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影响因子：
2.7
作者：
BECKER, JB;BEER, ME
通讯作者：
BEER, ME
DOI：
10.1073/pnas.1137864100
发表时间：
2003-06-10
影响因子：
11.1
作者：
Harley, VR;Layfield, S;Jans, DA
通讯作者：
Jans, DA
影响因子：
6.1
作者：
Cantuti-Castelvetri, Ippolita;Keller-McGandy, Christine;Standaert, David G.
通讯作者：
Standaert, David G.
影响因子：
--
作者：
Ely, Daniel;Milsted, Amy;Turner, Monte
通讯作者：
Turner, Monte
影响因子：
3.3
作者：
Ji, Jing;Dluzen, Dean E.
通讯作者：
Dluzen, Dean E.