Morris D J
Department of Pathology and Laboratory Medicine, Miriam Hospital, Providence, RI.
J Steroid Biochem Mol Biol. 1993 Apr;45(1-3):19-25. doi: 10.1016/0960-0760(93)90117-f.
Significant quantities of 5 alpha and 5 beta-Ring A-reduced metabolites and several polar cytochrome P-450 dependent hydroxylated neutral metabolites of aldosterone (Aldo) (NMA) are soon present in the kidney during the latent period, prior to the expression of Aldo's effects on Na+ and K+. Their levels in the kidney (a) correlate, in a dose-dependent manner, with the magnitude of physiological responses to Aldo in male rats, (b) are lower in the kidneys of females, which show smaller responses to Aldo than males, (c) are lower in the kidneys of males treated with the anti-mineralocorticoid spironolactone, and (d) their synthesis can be regulated by dietary Na+ and K+. Anti-mineralocorticoids completely inhibit synthesis of 5 alpha-reduced metabolites of Aldo in both kidney and toad bladder and of several of the polar hydroxylated NMA in both liver and kidney. 5 alpha-Reduced metabolites and their 2-hydroxylated derivatives possess significant mineralocorticoid activity and their synthesis is increased in rats fed a low Na+ diet and decreased with a high Na+ diet. We have suggested that their synthesis may play a major role in the expression and/or regulation of the individual renal anti-natriuretic and kaliuretic actions of Aldo.
在醛固酮（Aldo）对钠和钾产生作用的潜伏期内，肾脏中很快就会出现大量5α和5β-环A还原代谢产物以及几种极性的细胞色素P-450依赖性醛固酮羟基化中性代谢产物（NMA）。它们在肾脏中的水平：（a）与雄性大鼠对醛固酮的生理反应强度呈剂量依赖性相关；（b）在雌性大鼠肾脏中较低，雌性大鼠对醛固酮的反应比雄性大鼠小；（c）在用抗盐皮质激素螺内酯处理的雄性大鼠肾脏中较低；（d）其合成可受饮食中钠和钾的调节。抗盐皮质激素完全抑制肾脏和蟾蜍膀胱中醛固酮5α还原代谢产物的合成以及肝脏和肾脏中几种极性羟基化NMA的合成。5α还原代谢产物及其2-羟基化衍生物具有显著的盐皮质激素活性，在低钠饮食的大鼠中其合成增加，而在高钠饮食时则减少。我们认为它们的合成可能在醛固酮的个体肾脏抗利尿和排钾作用的表达和/或调节中起主要作用。
