Zager P G, Luetscher J A, Hsueh W A, Chavarri M R, Dowdy A J
J Clin Endocrinol Metab. 1979 Mar;48(3):441-50. doi: 10.1210/jcem-48-3-441.
The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements.
通过在多室模型中模拟皮质醇和醛固酮的分布、结合及代谢，分析肾上腺皮质对促肾上腺皮质激素（ACTH）输注的动态反应。该模型纳入了温度和皮质醇浓度对醛固酮在血浆中的结合以及在血浆和红细胞之间分布的影响，新的观察结果证实了这一点。皮质醇和醛固酮的分泌率根据内源性类固醇和注入示踪剂的血浆浓度系列测量值计算得出。通过静脉注射大剂量皮质醇后的观察结果对该模型进行了验证。19名正常志愿者在摄入含10毫当量钠的饮食的第4天接受研究。地塞米松抑制内源性ACTH，在4小时内以两种不同速率按不同顺序输注α-1-24ACTH。在持续输注ACTH的每小时期间，血浆皮质醇持续升高，而血浆醛固酮迅速上升，在20 - 30分钟内达到平台期。ACTH输注20 - 30分钟后，皮质醇分泌接近最大速率；血浆皮质醇的持续升高是由于与其他隔室的平衡缓慢所致。醛固酮分泌迅速上升至峰值，然后在ACTH输注20分钟后降至较低水平；在持续输注ACTH期间，分泌率维持在较低水平，在停止输注后几分钟内急剧下降。血浆类固醇对不同ACTH输注顺序反应的特征差异可通过醛固酮分泌的更快变化以及皮质醇和醛固酮不同的清除率来解释，清除率随血浆皮质醇浓度而变化。分离血液时的温度显著影响血浆醛固酮测量值。
