Ferrari P, Obeyesekere V R, Li K, Wilson R C, New M I, Funder J W, Krozowski Z S
Laboratory of Molecular Hypertension, Baker Medical Research Institute, Prahran, Melbourne, Australia.
Mol Cell Endocrinol. 1996 May 17;119(1):21-4. doi: 10.1016/0303-7207(96)03787-2.
The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol into mineralocorticoid receptor inactive cortisone, thus preventing occupation of the non-selective mineralocorticoid receptor by glucocorticoids in the kidney. Mutations generating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME), although proof of mutant protein synthesis was not provided. In the present study we have examined the metabolism of cortisol in mammalian cells transfected with plasmids expressing the wild type and mutant enzymes from three additional families of patients with mutations in the HSD11B2 gene. These studies revealed that the mutants were enzymatically inactive in intact mammalian cells expressing significant levels of both full length and truncated proteins. This is the first study to definitively show that point mutations in the HSD11B2 gene abolish 11 beta HSD2 enzymatic activity in the syndrome of AME.
II型11β-羟类固醇脱氢酶（11βHSD2）可将皮质醇转化为对盐皮质激素受体无活性的可的松，从而防止糖皮质激素占据肾脏中的非选择性盐皮质激素受体。在表观盐皮质激素增多症（AME）的先天性综合征中，已在HSD11B2基因中描述了产生无活性酶的突变，尽管未提供突变蛋白合成的证据。在本研究中，我们检测了用表达来自另外三个HSD11B2基因突变患者家族的野生型和突变型酶的质粒转染的哺乳动物细胞中皮质醇的代谢情况。这些研究表明，在表达大量全长和截短蛋白的完整哺乳动物细胞中，这些突变体在酶学上无活性。这是第一项明确表明HSD11B2基因中的点突变在AME综合征中消除11βHSD2酶活性的研究。
