Reaven E, Tsai L, Azhar S
Department of Medicine, Stanford University School of Medicine, CA, USA.
J Lipid Res. 1995 Jul;36(7):1602-17.
Although the 'selective' pathway is a major cholesteryl ester (CE) uptake pathway used by steroidogenic cells, essentially nothing is known about the itinerary of the CE once it is extracted from lipoproteins at the cell surface. In the current report we have begun to trace 'selective' pathway internalized-CE using both native and reconstituted human (h) high density lipoproteins (hHDL3) with variously labeled and tagged CEs to provide information from either a biochemical or morphological perspective. It appears that the amount of hHDL3-CE that is internalized and processed through the 'selective' pathway is directly related to the amount of cholesterol used for steroidogenesis at any given time point. There is a time-related correlation between the level of the Bt2cAMP-stimulated cell steroidogenic response, the level of conversion of freshly obtained hHDL3-CE into progestins, increases in hHDL3-derived CE internalization, hHDL3-CE hydrolysis, re-esterification and/or storage. None of this processing takes place in non-stimulated (non-Bt2cAMP treated) cells which do not secrete progestins despite the availability of hHDL3 as a cholesterol source. The data suggest that the 'selective' pathway has a special role in steroidogenic cells-one of providing sufficient cholesterol to fuel the required production of steroid hormones.
尽管“选择性”途径是类固醇生成细胞摄取胆固醇酯(CE)的主要途径,但对于CE一旦在细胞表面从脂蛋白中提取后的行程基本上一无所知。在本报告中,我们开始利用天然和重组的人(h)高密度脂蛋白(hHDL3)以及各种标记和标签的CE来追踪“选择性”途径内化的CE,以便从生化或形态学角度提供信息。似乎通过“选择性”途径内化和处理的hHDL3-CE的量与在任何给定时间点用于类固醇生成的胆固醇量直接相关。在Bt2cAMP刺激的细胞类固醇生成反应水平、新获得的hHDL3-CE转化为孕激素的水平、hHDL3衍生的CE内化增加、hHDL3-CE水解、再酯化和/或储存之间存在时间相关的相关性。尽管有hHDL3作为胆固醇来源,但在不分泌孕激素的未刺激(未用Bt2cAMP处理)细胞中,这些过程均未发生。数据表明,“选择性”途径在类固醇生成细胞中具有特殊作用——为类固醇激素的所需产生提供足够的胆固醇。