Vahouny G V, Chanderbhan R, Noland B J, Scallen T J
Endocr Res. 1984;10(3-4):473-505. doi: 10.1080/07435808409036512.
The cholesterol substrate required for sustained adrenal steroidogenesis is largely derived from the endogenous stores of cholesterol esters, which are located in large lipid inclusion droplets in the cytoplasm. In isolated adrenal cells, these esters are hydrolyzed during a variety of stimuli associated with cellular cAMP production. This largely appears to be a response to the action of a neutral cholesterol ester hydrolase, whose activity is modulated by phosphorylation of the enzyme protein, catalyzed by cAMP-dependent protein kinase. Transfer of the resulting unesterified cholesterol to mitochondria can be accomplished in a model system by sterol carrier protein2 (SCP2). This protein is distinct from fatty acid binding protein (FABP), has a Mr of 13,500 and is basic in nature. SCP2 can sequester cholesterol from lipid inclusion droplets in a stoichiometric relationship, and transfer this cholesterol to isolated adrenal mitochondria. SCP2 can also enhance the intermembrane transfer of mitochondrial cholesterol to cytochrome P 450scc, but does not directly affect cholesterol side chain cleavage. The stimulatory effect of adrenal cytosolic preparations on mitochondrial pregnenolone production can be completely abolished by pretreatment with anti SCP2 IgG.
持续肾上腺类固醇生成所需的胆固醇底物主要来源于胆固醇酯的内源性储存，这些胆固醇酯存在于细胞质中的大脂质包涵体滴中。在分离的肾上腺细胞中，这些酯在与细胞环磷酸腺苷（cAMP）产生相关的各种刺激过程中被水解。这在很大程度上似乎是对一种中性胆固醇酯水解酶作用的反应，该酶的活性受环磷酸腺苷依赖性蛋白激酶催化的酶蛋白磷酸化调节。在模型系统中，生成的未酯化胆固醇向线粒体的转移可通过固醇载体蛋白2（SCP2）完成。这种蛋白质与脂肪酸结合蛋白（FABP）不同，分子量为13500，本质上呈碱性。SCP2可以按化学计量关系从脂质包涵体滴中螯合胆固醇，并将这种胆固醇转移到分离的肾上腺线粒体中。SCP2还可以增强线粒体胆固醇向细胞色素P450scc的膜间转移，但不直接影响胆固醇侧链裂解。用抗SCP2免疫球蛋白G预处理可完全消除肾上腺胞质制剂对线粒体孕烯醇酮生成的刺激作用。
