Fehm H L, Voigt K H, Kummer G, Lang R, Pfeiffer E F
J Clin Invest. 1979 Feb;63(2):247-53. doi: 10.1172/JCI109296.
Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.
最近的研究表明，大鼠应激诱导促肾上腺皮质激素（ACTH）分泌存在双重皮质类固醇反馈机制。这种可能性促使我们研究肾上腺皮质功能减退继发的非应激性ACTH分泌过多患者中，给予皮质类固醇后ACTH水平抑制的动力学。根据不同方案给予皮质醇，这些方案旨在提供输入信号的极端变化。通过这种方式，可以区分ACTH水平抑制的两个阶段。只要血浆皮质醇水平升高，第一阶段的下降就会立即出现。皮质醇浓度增量的对数与每分钟ACTH水平的下降之间存在线性回归（r = 0.951）（差异或速率敏感反馈机制）。通过这种快速机制，皮质醇的绝对剂量和血浆皮质醇浓度均与ACTH的抑制程度没有密切相关性。ACTH水平的第二次下降在给予皮质类固醇后30分钟开始。在这种情况下，ACTH水平的抑制程度与皮质醇剂量之间存在显著的线性回归（r = 0.997）（积分或剂量敏感反馈机制）。地塞米松的剂量敏感反馈作用小于根据其相对抗炎效力所预测的作用。给予1.0或1.25 mg地塞米松时未观察到速率敏感效应。
