Elias P M, Williams M L, Maloney M E, Bonifas J A, Brown B E, Grayson S, Epstein E H
J Clin Invest. 1984 Oct;74(4):1414-21. doi: 10.1172/JCI111552.
The pathological scaling in recessive x-linked ichthyosis is associated with accumulation of abnormal quantities of cholesterol sulfate in stratum corneum (J. Clin. Invest. 68:1404-1410, 1981). To determine whether or not cholesterol sulfate accumulates in recessive x-linked ichthyosis as a direct result of the missing enzyme, steroid sulfatase, we quantitated both steroid sulfatase and its substrate, we quantitated both steroid sulfatase and its substrate, cholesterol sulfate, in different epidermal strata, as well as within stratum corneum subcellular fractions obtained from normal human and neonatal mouse epidermis and from patients with recessive x-linked ichthyosis. In normal human and mouse epidermis, steroid sulfatase activity peaked in the stratum granulosum and stratum corneum, and negligible activity was detectable in lower epidermal layers. In contrast, in recessive x-linked ichthyosis epidermis, enzyme levels were virtually undetectable at all levels. In normal human stratum corneum, up to 10 times more steroid sulfatase activity was present in purified peripheral membrane preparations than in the whole tissue. Whereas in normal human epidermis cholesterol sulfate levels were lowest in the basal/spinous layer, and highest in the stratum granulosum, in recessive x-linked ichthyosis the levels were only slightly higher in the lower epidermis, but continued to climb in the stratum corneum. In both normal and in recessive x-linked ichthyosis stratum corneum, cholesterol sulfate appeared primarily within membrane domains, paralleling the pattern of steroid sulfatase localization. Finally, the role of excess cholesterol sulfate in the pathogenesis of recessive x-linked ichthyosis was directly tested by topical applications of this substance, which produced visible scaling in hairless mice in parallel to an increased cholesterol sulfate content of the stratum corneum. These results demonstrate an intimate relationship between steroid sulfatase and cholesterol sulfate in normal epidermis: both are concentrated in the outer epidermis (stratum corneum and stratum granulosum), and both are localized to membrane domains. Presumably, as a result of this distribution pattern, continued enzymatic degradation of substrate occurs in normal epidermis, thereby preventing excessive accumulation of cholesterol sulfate. In contrast, in recessive x-linked ichthyosis, degradation of cholesterol sulfate does not occur and cholesterol sulfate accumulates specifically in the stratum corneum, where it produces visible scale.
隐性X连锁鱼鳞病的病理性鳞屑与角质层中硫酸胆固醇异常量的积累有关（《临床研究杂志》68:1404 - 1410，1981）。为了确定硫酸胆固醇在隐性X连锁鱼鳞病中积累是否是由于缺失的酶——类固醇硫酸酯酶直接导致的，我们对类固醇硫酸酯酶及其底物硫酸胆固醇进行了定量分析，这些分析在不同的表皮层以及从正常人和新生小鼠表皮及隐性X连锁鱼鳞病患者获得的角质层亚细胞组分中进行。在正常人和小鼠表皮中，类固醇硫酸酯酶活性在颗粒层和角质层达到峰值，而在较低的表皮层中检测到的活性可忽略不计。相比之下，在隐性X连锁鱼鳞病表皮中，在各个层面几乎都检测不到酶水平。在正常人的角质层中，纯化的外周膜制剂中的类固醇硫酸酯酶活性比整个组织中高多达10倍。在正常人表皮中，硫酸胆固醇水平在基底层/棘层最低，在颗粒层最高，而在隐性X连锁鱼鳞病中，其水平在较低表皮层仅略高，但在角质层中持续上升。在正常和隐性X连锁鱼鳞病的角质层中，硫酸胆固醇主要出现在膜结构域内，与类固醇硫酸酯酶的定位模式相似。最后，通过局部应用该物质直接测试了过量硫酸胆固醇在隐性X连锁鱼鳞病发病机制中的作用，这在无毛小鼠中产生了可见的鳞屑，同时角质层中硫酸胆固醇含量增加。这些结果表明在正常表皮中类固醇硫酸酯酶和硫酸胆固醇之间存在密切关系：两者都集中在外层表皮（角质层和颗粒层），并且都定位于膜结构域。据推测，由于这种分布模式，在正常表皮中底物持续进行酶促降解，从而防止硫酸胆固醇过度积累。相比之下，在隐性X连锁鱼鳞病中，硫酸胆固醇的降解不发生，并且硫酸胆固醇特异性地在角质层中积累，在那里它产生可见的鳞屑。
