Vogeser M, Zachoval R, Jacob K
Institute of Clinical Chemistry, Ludwig-Maximilians-Universität Munich, Klinikum Grosshadern, 81366, Munich, Germany.
Clin Biochem. 2001 Jul;34(5):421-5. doi: 10.1016/s0009-9120(01)00251-x.
11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes interconvert active cortisol and inactive cortisone. There is growing evidence that local tissue concentrations of cortisol are generally modulated by site specific different 11beta-HSD actions. While 11beta-HSD type 2 unidirectionally inactivates cortisol, type 1 isoform acts bidirectionally. 11beta-HSD type 1 is mainly localized in the liver and may thus restore circulating biologically inactive cortisone to active cortisol thereby modulating systemic glucocorticoid action; such a mechanism might be of importance in stressful situations. To study this hypothesis we investigated the influence of exogenous ACTH on serum cortisol/cortisone ratio.
Paired serum samples that were submitted for routine analysis of cortisol before and 1 h after stimulation with 250 microg ACTH (1-24) (Synacthen) were collected prospectively if the routine tests indicated normal adrenal function; 40 patients were included in the study, 29 patients were female, 11 male, median age was 31 yr (range 14-70). Serum cortisol and cortisone were determined using LC-ESI/MS/MS with an online sample extraction system and tri-deuterated cortisol as the internal standard.
While mean serum cortisol increased by 109% (mean basal concentration 373 nmol/L (SD 151 nmol/L), stimulated 781 nmol/L (SD 194 nmol/L)), mean serum cortisone significantly decreased after ACTH administration by 31% (p < 0.001, paired t-test for differences). Mean serum cortisone was 70 nmol/L (SD 16 nmol/L) before and 48 nmol (SD 16 nmol/L) after ACTH administration; decrease in serum cortisone was observed in 34 (85%) of the patients. The ratio of serum cortisol/cortisone increased in all subjects (mean 5.4 (SD 1.9) before ACTH, and 16.2 (SD 6.2) after ACTH; p < 0.001).
The data of our observational study suggest a modulation of peripheral metabolism of cortisol by ACTH with a stimulation of systemic 11beta-HSD type 1 activity, leading to restoration of inactive cortisone to biologically active cortisol.
11β-羟基类固醇脱氢酶（11β-HSD）可使活性皮质醇与无活性可的松相互转换。越来越多的证据表明，皮质醇在局部组织中的浓度通常受特定部位不同的11β-HSD作用调控。11β-HSD 2型单向使皮质醇失活，而1型同工酶则具有双向作用。11β-HSD 1型主要定位于肝脏，因此可能将循环中的无生物活性的可的松还原为活性皮质醇，从而调节全身糖皮质激素的作用；这种机制在应激情况下可能很重要。为了研究这一假说，我们调查了外源性促肾上腺皮质激素（ACTH）对血清皮质醇/可的松比值的影响。
如果常规检测显示肾上腺功能正常，则前瞻性收集在接受250μg ACTH（1-24）（合成促皮质素）刺激前及刺激后1小时用于皮质醇常规分析的配对血清样本；40例患者纳入研究，其中29例为女性，11例为男性，中位年龄为31岁（范围14-70岁）。采用液相色谱-电喷雾电离/串联质谱法（LC-ESI/MS/MS），以在线样本提取系统和氘代皮质醇作为内标物测定血清皮质醇和可的松。
虽然血清皮质醇均值增加了109%（基础平均浓度为373nmol/L（标准差151nmol/L），刺激后为781nmol/L（标准差194nmol/L）），但给予ACTH后血清可的松均值显著降低了31%（p<0.001，配对t检验差异）。给予ACTH前血清可的松均值为70nmol/L（标准差16nmol/L），给药后为48nmol（标准差16nmol/L）；34例（85%）患者血清可的松降低。所有受试者血清皮质醇/可的松比值均升高（ACTH给药前均值为5.4（标准差1.9），给药后为16.2（标准差6.2）；p<0.001）。
我们的观察性研究数据表明，ACTH可调节皮质醇的外周代谢，刺激全身11β-HSD 1型活性，导致无活性可的松还原为生物活性皮质醇。
