Nishikawa T, Mikami K, Saito Y, Tamura Y, Yoshida S
Department of Internal Medicine, Chiba University School of Medicine, Japan.
Endocrinology. 1988 Mar;122(3):877-83. doi: 10.1210/endo-122-3-877.
Previous studies clearly demonstrated that cells isolated from the chromatically distinct inner (primarily zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex have vastly different steroidogenic capabilities; the outer zone produces far more cortisol than the inner zone, and mitochondrial cholesterol side-chain cleavage activity in the inner zone is not modulated by ACTH. Thus, in this study we have investigated the characteristics and properties of cholesterol ester hydrolase (CEHase) and acyl-coenzyme-A/cholesterol acyltransferase (ACAT) in the outer and inner zones of the guinea pig adrenal to clarify the zonal difference in cholesterol metabolism. CEHase showed two pH optima at around pH 4.5 and pH 7.5 in the outer zone, while optimum activity in the inner zone was found only around pH 4.5, suggesting a lack of neutral CEHase in the inner zone. The acid CEHase was found mainly in the lysosomal fraction, and the neutral CEHase was located mainly in the microsomal fraction. The neutral CEHase activity in the outer zone was significantly enhanced by ether stress, while the acid CEHase activity was not changed in either of the two zones by stress. The basal activity of ACAT was significantly higher in the outer zone than in the inner zone. The present experiments also demonstrated that the inner zone always showed lower ACAT activity than the outer zone even when added cholesterol exogenously. It is suggested that the relatively low activity of ACAT may not always be explained by the reduced content of cholesterol in the microsomal fraction of zona reticularis. ACAT activity in the outer zone was significantly decreased by ether-induced stress, but that in the inner zone was not changed. The content of esterified cholesterol in whole homogenate and the microsomal fraction was significantly decreased in the outer zone, but not in the inner zone, by ether stress. Thus, the decrease in esterified cholesterol after ether stress seems to relate to increased neutral CEHase activity and decreased ACAT activity in the outer zone. The present observation clearly indicates that the lack of neutral CEHase and the lesser activity of ACAT in the inner zone than in the outer zone may contribute to the impaired cholesterol metabolism in the inner zone.
先前的研究清楚地表明，从豚鼠肾上腺皮质颜色不同的内层（主要是网状带）和外层（束状带和球状带）分离出的细胞具有截然不同的类固醇生成能力；外层产生的皮质醇比内层多得多，并且内层的线粒体胆固醇侧链裂解活性不受促肾上腺皮质激素（ACTH）的调节。因此，在本研究中，我们研究了豚鼠肾上腺外层和内层中胆固醇酯水解酶（CEHase）和酰基辅酶A/胆固醇酰基转移酶（ACAT）的特性和性质，以阐明胆固醇代谢的区域差异。CEHase在肾上腺外层显示出两个pH最佳值，分别在pH 4.5和pH 7.5左右，而在内层仅在pH 4.5左右发现最佳活性，这表明内层缺乏中性CEHase。酸性CEHase主要存在于溶酶体部分，而中性CEHase主要位于微粒体部分。肾上腺外层的中性CEHase活性在乙醚应激下显著增强，而酸性CEHase活性在两个区域中均未因应激而改变。ACAT的基础活性在外层显著高于内层。本实验还表明，即使外源性添加胆固醇，内层的ACAT活性始终低于外层。这表明ACAT活性相对较低可能并不总是由网状带微粒体部分中胆固醇含量的降低来解释。肾上腺外层ACAT活性在乙醚诱导的应激下显著降低，但内层的ACAT活性未改变。乙醚应激使肾上腺外层全匀浆和微粒体部分中酯化胆固醇的含量显著降低，但内层未降低。因此，乙醚应激后酯化胆固醇的减少似乎与外层中性CEHase活性增加和ACAT活性降低有关。目前的观察清楚地表明，内层缺乏中性CEHase以及ACAT活性低于外层可能导致内层胆固醇代谢受损。
