Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action
Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action
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盐皮质激素明显过量、假性醛固酮增多症和尿电解质排泄：重新定义盐皮质激素作用
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发表时间：
1990
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通讯作者：
L. Roy
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作者：
J. Funder;P. Pearce;K. Myles;L. Roy
有明显盐皮质激素过多的患者11βOH类固醇脱氢酶(11SD)活性低或缺乏，肾内皮质醇水平过高导致Na+滞留和高血压。假性低醛固酮增多症(PHA)则以高醛固酮血症时的盐耗为特征，反映盐皮质激素受体(MR)减少或缺失。虽然AME被认为反映了MR皮质醇的不当占用，但一些特征也提示糖皮质激素受体(GR)的不当占用。为了测试这种可能性，我们给四名PHA患者服用了已知的阻断11SD的甘苯氧酮，并观察到显著的盐皮质激素作用，例如，抗心绞痛和血浆碳酸氢盐升高。为了进一步验证肾GR占位是否可能引起经典的糖皮质激素反应，我们给去肾上腺的大鼠注射了高度特异的糖皮质激素RU 28362，结果表明它有明显的抗心房利钠作用。最后，通过用RU 28318或RU 38486选择性地阻断MR或GR，我们证明了大鼠的生理性糖皮质激素皮质酮通过MR或GR占据而对肾上腺切除的大鼠有抗心房利钠的作用。以前的研究清楚地表明，MR是天生的非选择性的，对醛固酮、皮质酮和皮质醇具有同等的内在亲和力。目前的研究表明，这种非选择性包括核反应元件，MR或GR可能与其结合以引起盐皮质激素效应，并进一步强调了11SD酶在醛固酮特定的盐皮质激素作用中的重要性。-Funderd，J.W.；Pearce，P.T.；Myles，K.；Roy，L.P.明显的盐皮质激素过量，假性低醛固酮症，以及尿液电解质排泄：朝着重新定义盐皮质激素作用的方向。FASE B J.4：3234-3238；1990。
Patients with apparent mineralocorticoid excess (AME) have low or absent activity of the enzyme 11βOH steroid dehydrogenase (11SD), and inappropriately high intrarenal levels of cortisol resulting in Na+ retention and hypertension. Pseudohypoaldosteronism (PHA), in contrast, is characterized by salt wasting despite hyperaldosteronemia, reflecting low or absent mineralocorticoid receptors (MR). Although AME is presumed to reflect inappropriate cortisol occupancy of MR, several features also suggest inappropriate occupancy of glucocorticoid receptors (GR). To test this possibility, we administered carbenoxolone, which is known to block 11SD, to four patients with PHA, and observed marked mineralocorticoid effects, e.g., antinatriuresis and elevated plasma bicarbonate. To further test the possibility that occupancy of renal GR may induce a classical mineralocorticoid response, we administered the highly specific glucocorticoid RU 28362 to adrenalectomized rats and showed that it has profound antinatriuretic effects. Finally, by selectively blocking MR with RU 28318 or GR with RU 38486, we have shown that corticosterone, the physiologic glucocorticoid in rats, has an antinatriuretic effect in adrenalectomized rats via either MR or GR occupancy. Previous studies have clearly shown that MR are inherently nonselective and have equivalent intrinsic affinity for aldosterone, corticosterone, and cortisol. The present studies suggest that this non‐selectivity includes the nuclear response element to which either MR or GR may bind to elicit a mineralocorticoid effect, and further underscore the importance of the enzyme 11SD in the specific mineralocorticoid action of aldosterone.— Funder, J. W.; Pearce, P. T.; Myles, K.; Roy, L. P. Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action. FASEB J. 4: 3234‐3238; 1990.