Weidenfeld J, Itzik A, Feldman S
Department of Neurology, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Brain Res. 1997 Apr 18;754(1-2):187-94. doi: 10.1016/s0006-8993(97)00078-4.
In the present study we examined the negative feedback effect of exogenous and endogenous glucocorticoids (GC) on the responses of the hypothalamo-pituitary-adrenocortical (HPA) axis to electrical stimulation of the central amygdaloid nucleus (AMG) and the ventral noradrenergic bundle (VNAB). Injection of dexamethasone (DEX 5-50 microg/kg BW) 3.5 h prior to the electrical stimuli inhibited the serum ACTH and corticosterone (CS) responses in a dose dependent manner. At a dose of 50 microg/kg BW DEX, the stress induced responses was completely abolished. Pretreatment with a subcutaneous injection of corticosteroid type II receptor antagonist (RU-38486) 30 mg/kg BW, enhanced the ACTH and CS responses to both stimuli. In contrast, the type I receptor antagonist (RU-28381) did not affect neither the responses to both stimuli nor the inhibitory effect exerted by DEX. Electrical stimulation of both the AMG and VNAB caused a significant depletion of CRF-41 content of the median eminence (ME). Pretreatment with DEX (50 microg/kg BW) inhibited the electrical stimuli-induced depletion of ME CRH-41. These results suggest that: (1) the HPA axis responses to electrical stimuli of the AMG and the VNAB are sensitive to the negative feedback of GC; (2) the feedback effect exerted by GC is mediated by type II GC receptors; (3) CRH-41 released from the ME plays a dynamic role in mediating pituitary-adrenocortical responses to the electrical stimuli; (4) the inhibitory effect of exogenous DEX is mediated by a reduction of CRF-41 release from the ME.
在本研究中,我们检测了外源性和内源性糖皮质激素(GC)对下丘脑 - 垂体 - 肾上腺皮质(HPA)轴对中央杏仁核(AMG)和腹侧去甲肾上腺素能束(VNAB)电刺激反应的负反馈作用。在电刺激前3.5小时注射地塞米松(DEX 5 - 50微克/千克体重),以剂量依赖方式抑制血清促肾上腺皮质激素(ACTH)和皮质酮(CS)反应。在50微克/千克体重的DEX剂量下,应激诱导的反应被完全消除。皮下注射皮质类固醇II型受体拮抗剂(RU - 38486)30毫克/千克体重预处理,增强了对两种刺激的ACTH和CS反应。相比之下,I型受体拮抗剂(RU - 28381)既不影响对两种刺激的反应,也不影响DEX施加的抑制作用。对AMG和VNAB两者的电刺激均导致正中隆起(ME)中促肾上腺皮质激素释放因子(CRF) - 41含量显著减少。DEX(50微克/千克体重)预处理抑制了电刺激诱导的ME促肾上腺皮质激素释放激素(CRH) - 41的减少。这些结果表明:(1)HPA轴对AMG和VNAB电刺激的反应对GC的负反馈敏感;(2)GC施加的反馈作用由II型GC受体介导;(3)从ME释放的CRH - 41在介导垂体 - 肾上腺皮质对电刺激的反应中起动态作用;(4)外源性DEX的抑制作用是通过减少ME中CRF - 41的释放来介导的。