Ferrari P, Smith R E, Funder J W, Krozowski Z S
Baker Medical Research Institute, Melbourne, Australia.
Am J Physiol. 1996 May;270(5 Pt 1):E900-4. doi: 10.1152/ajpendo.1996.270.5.E900.
The 11 beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme is thought to confer specificity on the mineralocorticoid receptor by inactivating glucocorticoids in mineralocorticoid target organs. The cloned 11 beta HSD2 displayed Michaelis constant values for corticosterone and cortisol of 5.1 and 61 nM, respectively. Linearity in the dose-response curve ranged between 1 and 200 nM for corticosterone and 25 and 2,000 nM for cortisol, with no evidence for complex kinetics. Inhibition of cortisol oxidation by other steroids was purely competitive in nature. Inhibition of 11 beta HSD2 activity by the end product or aldosterone occurred only at supraphysiological levels, whereas corticosterone and deoxycorticosterone displayed significant inhibition at physiological concentrations and progesterone at concentrations that occur during pregnancy. In intact transfected CHOP cells, dexamethasone was converted to 11-dehydrodexamethasone by 11 beta HSD2 but not type 1 11 beta-hydroxysteroid dehydrogenase, an aspect that may be useful in evaluating 11 beta HSD activity in intact cells.
2型11β-羟基类固醇脱氢酶（11βHSD2）被认为可通过使盐皮质激素靶器官中的糖皮质激素失活，赋予盐皮质激素受体特异性。克隆的11βHSD2对皮质酮和皮质醇的米氏常数分别为5.1和61 nM。皮质酮的剂量反应曲线线性范围在1至200 nM之间，皮质醇的剂量反应曲线线性范围在25至2000 nM之间，未发现复杂动力学的证据。其他类固醇对皮质醇氧化的抑制本质上完全是竞争性的。终产物或醛固酮对11βHSD2活性的抑制仅在超生理水平出现，而皮质酮和脱氧皮质酮在生理浓度时显示出显著抑制，孕酮在妊娠期间出现的浓度时显示出显著抑制。在完整的转染CHOP细胞中，地塞米松被11βHSD2转化为11-脱氢地塞米松，但不被1型11β-羟基类固醇脱氢酶转化，这一点在评估完整细胞中的11βHSD活性时可能有用。
