The reverse cholesterol transport system as a potential mediator of luteolysis in the primate corpus luteum.
The reverse cholesterol transport system as a potential mediator of luteolysis in the primate corpus luteum.
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DOI：
10.1530/rep-09-0005
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Hennebold JD
中科院分区：
文献类型：
--
作者：
Bogan RL;Hennebold JD
孕酮(P4)的产生停止(即功能退化)，是灵长类黄体黄体溶解的关键事件，但人们对此知之甚少。以前，我们发现在恒河猴CL的自发功能退化过程中，参与胆固醇摄取的编码蛋白的基因减少，而参与胆固醇流出的基因(反向胆固醇运输；RCT)的表达增加，从而潜在地耗尽类固醇生成所需的胆固醇储备。因此，对随机对照试验的必要组成部分进行了全面分析。RCT组分在猕猴CL中表达，包括胆固醇感受器(肝脏×受体α或NR1H3；以及β或NR1H2)、外流蛋白(三磷酸腺苷结合盒亚家族A1或ABCA1；以及G1或Abcg1)、受体(载脂蛋白A1或载脂蛋白A1；以及载脂蛋白E或载脂蛋白E)以及促进高密度脂蛋白形成的血浆蛋白(卵磷脂：胆固醇酰基转移酶或磷脂转移蛋白或磷脂转移蛋白)。ABCA1、APOE、PLTP和NR1H3在功能退化期的表达(mRNA和/或蛋白)增加，而脂蛋白受体表达减少。APOA1和APOE以及NR1H3在CL和参与调节胆固醇稳态的组织中表达最强。免疫定位研究表明，RCT蛋白和脂蛋白受体在大的黄体细胞中表达，黄体细胞在孕酮合成期间具有细胞内胆固醇储备。脂质染色显示功能退化后黄体胆固醇酯/脂分布的变化。这些结果表明，减少胆固醇摄取和增加RCT可能是限制类固醇合成所需的细胞内胆固醇池，从而启动灵长类黄体溶解的关键。
The cessation of progesterone (P4) production (i.e., functional regression), arguably the key event in luteolysis of the primate corpus luteum (CL), is poorly understood. Previously, we found that genes encoding proteins involved in cholesterol uptake decreased while those involved in cholesterol efflux (reverse cholesterol transport; RCT) increased in expression during spontaneous functional regression of the rhesus macaque CL, thereby potentially depleting the cholesterol reserves needed for steroidogenesis. Therefore, a comprehensive analysis of the components necessary for RCT was performed. RCT components were expressed (mRNA and/or protein) in the macaque CL including cholesterol sensors (liver × receptors α or NR1H3; and β or NR1H2), efflux proteins (ATP-binding cassette subfamilies A1 or ABCA1; and G1 or ABCG1), acceptors (apolipoproteins A1 or APOA1; and E or APOE), and plasma proteins facilitating high-density lipoprotein (HDL) formation (lecithin:cholesterol acyltransferase or LCAT; phospholipid transfer protein or PLTP). ABCA1, APOE, PLTP and NR1H3 increased, while lipoprotein receptors decreased, in expression (mRNA and/or protein) through the period of functional regression. The expression of APOA1 and APOE, as well as NR1H3, was greatest in the CL and tissues involved in regulating cholesterol homeostasis. Immunolocalization studies revealed that RCT proteins and lipoprotein receptors were expressed in large luteal cells, which possess intracellular cholesterol reserves during periods of progesterone synthesis. Lipid staining revealed changes in luteal cholesterol ester/lipid distribution that occurred following functional regression. These results indicate that decreased cholesterol uptake and increased RCT may be critical for the initiation of primate luteolysis by limiting intracellular cholesterol pools required for steroidogenesis.