Jacobson L, Sapolsky R
Department of Biological Sciences, Stanford University, CA 94305-5020.
Neuroendocrinology. 1993 Oct;58(4):420-9. doi: 10.1159/000126571.
Adrenalectomized rats replaced with constant, physiological levels of corticosterone via a subcutaneous pellet (Pellet) have normal basal morning ACTH but exhibit enhanced and prolonged ACTH responses to stress vs. sham-operated (Sham) rats. It has not been determined if the lack of either stress-induced or circadian increases in corticosterone, both of which are missing in Pellet rats, may account for this enhanced response. To test the extent to which stress-associated increases in corticosterone alone can normalize stress-induced hypersecretion of ACTH, we approximated endogenous secretion by injecting additional corticosterone in Pellet rats via an indwelling subcutaneous cannula, 5 min before hypoxia stress (10% O2). A corticosterone dose of 666 micrograms/kg (Pellet+B), but not 333 micrograms/kg (Pellet+Low B), produced plasma corticosterone levels comparable to those in Shams and normalized stress-induced but not post-stress plasma ACTH. Administration of the type II corticosteroid receptor antagonist RU 38486 30 min before corticosterone reversed this inhibition. We conclude that enhanced ACTH responses to stress in Pellet rats result in large part from lack of type II receptor-mediated feedback inhibition by corticosterone increases during stress, although prior circadian increases in corticosterone may also be required.
通过皮下植入物给予恒定生理水平皮质酮的肾上腺切除大鼠（植入物组）具有正常的基础晨促肾上腺皮质激素（ACTH）水平，但与假手术大鼠（假手术组）相比，对应激的ACTH反应增强且持续时间延长。尚未确定应激诱导的或昼夜节律性的皮质酮增加的缺乏（这两者在植入物组大鼠中均不存在）是否可解释这种增强的反应。为了测试仅应激相关的皮质酮增加在多大程度上可以使应激诱导的ACTH分泌过多正常化，我们通过在缺氧应激（10% O₂）前5分钟经皮下留置套管向植入物组大鼠注射额外的皮质酮来模拟内源性分泌。666微克/千克的皮质酮剂量（植入物组+高剂量皮质酮）可产生与假手术组相当的血浆皮质酮水平，并使应激诱导的但非应激后血浆ACTH正常化，而333微克/千克的剂量（植入物组+低剂量皮质酮）则无此效果。在注射皮质酮前30分钟给予II型糖皮质激素受体拮抗剂RU 38486可逆转这种抑制作用。我们得出结论，植入物组大鼠对应激的ACTH反应增强很大程度上是由于应激期间缺乏皮质酮增加所介导的II型受体反馈抑制，尽管先前昼夜节律性的皮质酮增加可能也是必需的。
