Abou-Samra A B, Catt K J, Aguilera G
Endocrinology. 1986 Sep;119(3):972-7. doi: 10.1210/endo-119-3-972.
The inhibition of ACTH secretion by glucocorticoids in vivo is biphasic, with rapid early suppression followed by transient recovery and a late inhibitory phase. To evaluate whether this biphasic effect of glucocorticoids occurs at the pituitary level, the effects of corticosterone (B) on stimulated ACTH release were analyzed in rat anterior pituitary cell cultures. Preincubation with 1 microM B inhibited the ACTH response to 10 nM CRF in a biphasic manner, with rapid inhibition after 10-40 min of preincubation, followed by partial recovery between 40-80 min, and a later phase of inhibition after 80-140 min. Preincubation with B for 40 or 120 min caused a dose-dependent suppression of CRF-stimulated ACTH release, with ED50 values of 416 +/- 21 and 45 +/- 12 nM B, respectively. Pretreatment with B also caused a biphasic inhibitory effect on the stimulatory action of vasopressin, angiotensin II, and norepinephrine on ACTH release. However, addition of these stimuli in combination with CRF surmounted B inhibition of CRF-stimulated ACTH release. B also inhibited the ACTH-releasing effects of postreceptor stimuli, including 8-bromo-cAMP, phorbol 12-myristate 13-acetate, and 1,2-dioctanoylglycerol. In the presence of cycloheximide (10 microM), the early inhibitory effect of B was unchanged, but the delayed effect was decreased. Whereas preincubation with B for 40 min inhibited ACTH release, but not total intracellular plus released ACTH, preincubation for 120 min decreased both released and total ACTH. These findings demonstrate that the two inhibitory effects of B on ACTH release differ in their kinetics, steroid sensitivity, and dependence on protein synthesis. The inhibitory effect of B on ACTH responses to stimuli with different mechanisms of action suggests that the suppressive effects of B are mainly exerted at a site distal to the formation of the second messengers involved in hormonal activation of ACTH release.
糖皮质激素在体内对促肾上腺皮质激素（ACTH）分泌的抑制作用是双相的，早期迅速抑制，随后短暂恢复，接着进入晚期抑制阶段。为评估糖皮质激素的这种双相作用是否发生在垂体水平，在大鼠垂体前叶细胞培养物中分析了皮质酮（B）对刺激的ACTH释放的影响。用1μM B预孵育以双相方式抑制ACTH对10 nM促肾上腺皮质激素释放因子（CRF）的反应，预孵育10 - 40分钟后迅速抑制，40 - 80分钟之间部分恢复，80 - 140分钟后进入后期抑制阶段。用B预孵育40或120分钟导致CRF刺激的ACTH释放呈剂量依赖性抑制，B的半数有效剂量（ED50）值分别为416±21和45±12 nM。用B预处理对血管加压素、血管紧张素II和去甲肾上腺素刺激ACTH释放的作用也产生双相抑制作用。然而，将这些刺激与CRF联合添加可克服B对CRF刺激的ACTH释放的抑制。B还抑制包括8 - 溴 - 环磷酸腺苷（8 - bromo - cAMP）、佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（phorbol 12 - myristate 13 - acetate）和1,2 - 二辛酰甘油（1,2 - dioctanoylglycerol）在内的受体后刺激对ACTH的释放作用。在存在放线菌酮（10μM）的情况下，B的早期抑制作用未改变，但延迟作用减弱。虽然用B预孵育40分钟抑制ACTH释放，但不抑制细胞内加释放的ACTH总量，预孵育120分钟则使释放的ACTH和ACTH总量均减少。这些发现表明，B对ACTH释放的两种抑制作用在动力学、类固醇敏感性和对蛋白质合成的依赖性方面存在差异。B对具有不同作用机制的刺激的ACTH反应的抑制作用表明，B的抑制作用主要在参与ACTH释放激素激活的第二信使形成的远端位点发挥。
