Kornel L, Miyabo S, Saito Z
J Clin Endocrinol Metab. 1975 Jun;40(6):949-58. doi: 10.1210/jcem-40-6-949.
Results of our previous studies revealed a derangement in the peripheral metabolism of adrenal steroids in patients with essential hypertension. To investigate further this finding, all indIVidual free and conjugated metabolites of cortisol were isolated, identified and quantitated in plasma of 14 normotensive subjects and 13 patients with benign, uncomplicated essential hypertension, following iv administration of a tracer dose of [4-14-C] cortisol. In addition, plasma levels of endogenous cortisol were determined at 8 AM and 4 PM in all the subjects examined. The results obtained revealed the following statistically significant differences between normotensives and hypertensives: 1) Mean plasma concentrations of cortisol metabolites reduced in ring-A with nonreduced 20-ketone, tetrahydrocortisol, tetrahydrocortisone, and their 5alpha-epimers, were 30% lower in the hypertensives; since these steroids constitute the bulk of the major group of cortisol metabolites--the glucuronide conjugates, plasma levels of this group of conjugates measured in toto were also found to be significantly lower in the hypertensives. 2) Concentrations of cortisol metabolites with non-reduced ring-A (delta-4-3-keto configuration preserved) but with reduced 20-ketone and/or hydroxylated at C-6, 20alpha- and 20beta- dihydrocortisol, 6alpha- and 6beta-hydroxycortisol, and 6-hydroxy-20-dihydrocortisol (all 4 isomers), were 73%, 48% and 68% respectively, higher in the hypertensives; since these steroids constitute the bulk of the sulfate-conjugated and nucleoside-complexed metabolites of cortisol, plasma levels of these groups of metabolites, measured in toto, were also found to be higher in the hypertensives. No significant difference was found between normotensives and hypertensives in the AM and PM plasma levels of cortisol. These findings, in conjunction with the results of our studies on urinary corticosteroid metabolites, which yielded identical findings, provide evidence for a decreased activity of hepatic cortisol-delta-4-hydrogenase enzyme system and increased activities (presumably compensatorily) of cortisol-20-reductase and 6-hydroxylase enzyme systems in patients with essential hypertension. The interrelation of these findings with those of other investigators studying steroid metabolites in hypertension, points to the corticosteroid metabolizing enzymes may be an etiological factor in essential hypertension.
我们之前研究的结果显示，原发性高血压患者肾上腺类固醇的外周代谢紊乱。为了进一步研究这一发现，在静脉注射微量[4-¹⁴C]皮质醇后，对14名血压正常的受试者和13名患有良性、无并发症的原发性高血压患者血浆中的所有皮质醇游离和结合代谢物进行了分离、鉴定和定量。此外，在所有接受检查的受试者中，于上午8点和下午4点测定了内源性皮质醇的血浆水平。所获得的结果显示，血压正常者与高血压患者之间存在以下具有统计学意义的差异：1）在高血压患者中，A环未还原、20-酮未还原的皮质醇代谢物、四氢皮质醇、四氢可的松及其5α-差向异构体的平均血浆浓度降低了30%；由于这些类固醇构成了皮质醇代谢物主要组群——葡萄糖醛酸结合物的大部分，因此在高血压患者中，总体测定的这一组结合物的血浆水平也显著降低。2）A环未还原（保留δ-4-3-酮构型）但20-酮还原和/或在C-6位羟基化的皮质醇代谢物、20α-和20β-双氢皮质醇、6α-和6β-羟基皮质醇以及6-羟基-20-双氢皮质醇（所有4种异构体）的浓度，在高血压患者中分别高出73%、48%和68%；由于这些类固醇构成了皮质醇的硫酸酯结合物和核苷复合代谢物的大部分，因此总体测定的这些组代谢物的血浆水平在高血压患者中也较高。血压正常者与高血压患者上午和下午血浆皮质醇水平之间未发现显著差异。这些发现，连同我们对尿皮质类固醇代谢物研究的结果（得出了相同的发现），为原发性高血压患者肝皮质醇-δ-4-脱氢酶系统活性降低以及皮质醇-20-还原酶和6-羟化酶系统活性增加（推测为代偿性）提供了证据。这些发现与其他研究高血压中类固醇代谢物的研究者的发现之间的相互关系表明，皮质类固醇代谢酶可能是原发性高血压的一个病因因素。
