Latif S A, McDermott M J, Morris D J
Steroids. 1983 Sep;42(3):283-97. doi: 10.1016/0039-128x(83)90040-5.
The synthesis of polar aldosterone metabolites by rat liver microsomes at physiological concentrations of aldosterone (21.5 nM), was markedly inhibited by progesterone, testosterone, corticosterone, K+-canrenoate and estradiol-17 beta. In contrast, corticosterone and estradiol-17 beta significantly increased the synthesis of reduced aldosterone metabolites by 8- and 15-fold respectively, the majority of which were 5 alpha-reduced products of aldosterone. In experiments at higher substrate (aldosterone) concentrations (20-200 microM) the synthesis of ring A-reduced aldosterone metabolites by liver microsomes followed Michaelis-Menten kinetics with a Km[app] for aldosterone of 160 microM and Vmax[app] of 12.2 nmoles/mg protein/5 min. In these experiments progesterone, testosterone and K+-canrenoate all competitively inhibited the synthesis of reduced metabolites with inhibition constants (Ki [app]) of 70, 85 and 55 microM respectively; however, corticosterone did not. In contrast, estradiol-17 beta increased the rate of synthesis of reduced products by 40%, lowering the Km[app] to 83 microM.
在醛固酮生理浓度（21.5 nM）下，大鼠肝微粒体合成极性醛固酮代谢产物的过程受到孕酮、睾酮、皮质酮、钾-坎利酸钾和雌二醇-17β的显著抑制。相比之下，皮质酮和雌二醇-17β分别使还原型醛固酮代谢产物的合成显著增加了8倍和15倍，其中大部分是醛固酮的5α-还原产物。在更高底物（醛固酮）浓度（20 - 200 μM）的实验中，肝微粒体合成A环还原型醛固酮代谢产物遵循米氏动力学，醛固酮的表观米氏常数（Km[app]）为160 μM，最大反应速度（Vmax[app]）为12.2纳摩尔/毫克蛋白质/5分钟。在这些实验中，孕酮、睾酮和钾-坎利酸钾均竞争性抑制还原型代谢产物的合成，抑制常数（表观抑制常数Ki [app]）分别为70、85和55 μM；然而，皮质酮没有。相反，雌二醇-17β使还原产物的合成速率提高了40%，将表观米氏常数（Km[app]）降至83 μM。
