Hoeg J M, Loriaux L, Gregg R E, Green W R, Brewer H B
Metabolism. 1985 Feb;34(2):194-7. doi: 10.1016/0026-0495(85)90132-5.
The cholesterol required for steroidogenesis may be provided by the novo biosynthesis or through the delivery of cholesterol by the circulating lipoproteins. By studying adrenocortical function, structure and biosynthetic capacity in an animal model devoid of the classical, high-affinity low density lipoprotein (LDL) receptor pathway, the respective roles of de novo cholesterolgenesis and lipoprotein cholesterol delivery were investigated. The Watanabe Heritable Hyperlipemic (WHHL) rabbit lacks the LDL-receptor pathway. The activity of the rate-limiting enzyme in cholesterolgenesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was 4- to 15-fold greater than normal in the WHHL adrenal gland. The basal corticosterone concentrations were normal in the WHHL rabbit; however, the corticosterone concentration increased by less than 50% of normal after an intravenous ACTH injection. Electron-microscopic evaluation of adrenocortical cells from the WHHL rabbits disclosed significantly increased mitochondrial surface area and diminished amounts of cytosolic lipid and lysosomal area. These data indicate that the mammalian adrenal gland utilizes endogenously synthesized cholesterol as well as cholesterol delivered through the LDL-receptor pathway. Moreover, in the absence of the LDL-receptor pathway, endogenously produced cholesterol is sufficient for normal basal glucocorticoid function.
类固醇生成所需的胆固醇可通过从头生物合成或循环脂蛋白输送胆固醇来提供。通过在缺乏经典的高亲和力低密度脂蛋白（LDL）受体途径的动物模型中研究肾上腺皮质功能、结构和生物合成能力，研究了从头胆固醇生成和脂蛋白胆固醇输送各自的作用。渡边遗传性高脂血症（WHHL）兔缺乏LDL受体途径。在WHHL肾上腺中，胆固醇生成限速酶3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的活性比正常高4至15倍。WHHL兔的基础皮质酮浓度正常；然而，静脉注射促肾上腺皮质激素（ACTH）后，皮质酮浓度的增加不到正常水平的50%。对WHHL兔肾上腺皮质细胞的电子显微镜评估显示，线粒体表面积显著增加，胞质脂质和溶酶体面积减少。这些数据表明，哺乳动物肾上腺利用内源性合成的胆固醇以及通过LDL受体途径输送的胆固醇。此外，在缺乏LDL受体途径的情况下，内源性产生的胆固醇足以维持正常的基础糖皮质激素功能。
