Diorio D, Viau V, Meaney M J
Douglas Hospital Research Center, Department of Psychiatry, Montréal, Canada.
J Neurosci. 1993 Sep;13(9):3839-47. doi: 10.1523/JNEUROSCI.13-09-03839.1993.
In the studies reported here we have examined the role of the medial prefrontal cortex (MpFC) in regulating hypothalamic-pituitary-adrenal (HPA) activity under basal and stressful conditions. In preliminary studies we characterized corticosteroid receptor binding in the rat MpFC. The results revealed high-affinity (Kd approximately 1 nM) binding with a moderate capacity (42.9 +/- 3 fmol/mg) for 3H-aldosterone (with a 50-fold excess of cold RU28362; mineralocorticoid receptor) and high-affinity (Kd approximately 0.5-1.0 nM) binding with higher capacity (183.2 +/- 22 fmol/mg) for 3H-RU 28362 (glucocorticoid receptor). Lesions of the MpFC (cingulate gyrus) significantly increased plasma levels of both adrenocorticotropin (ACTH) and corticosterone (CORT) in response to a 20 min restraint stress. The same lesions had no effect on hormone levels following a 2.5 min exposure to ether. Implants of crystalline CORT into the same region of the MpFC produced a significant decrease in plasma levels of both ACTH and CORT with restraint stress, but again, there was no effect with ether stress. Neither MpFC lesions nor CORT implants had any consistent effect on A.M. or P.M. levels of plasma ACTH or CORT. Manipulations of MpFC function were not associated with changes in the clearance rate for CORT or in corticosteroid receptor densities in the pituitary, hypothalamus, hippocampus, or amygdala. Taken together, these findings suggest that MpFC is a target site for the negative-feedback effects of glucocorticoids on stress-induced HPA activity, and that this effect is dependent upon the nature of the stress.
在本文报道的研究中，我们研究了内侧前额叶皮质（MpFC）在基础和应激条件下调节下丘脑 - 垂体 - 肾上腺（HPA）活动中的作用。在初步研究中，我们对大鼠MpFC中的皮质类固醇受体结合进行了表征。结果显示，对于³H - 醛固酮（冷RU28362过量50倍；盐皮质激素受体），存在高亲和力（解离常数Kd约为1 nM）结合且具有中等容量（42.9±3 fmol/mg），对于³H - RU 28362（糖皮质激素受体），存在高亲和力（Kd约为0.5 - 1.0 nM）结合且具有更高容量（183.2±22 fmol/mg）。MpFC（扣带回）损伤后，在20分钟的束缚应激下，促肾上腺皮质激素（ACTH）和皮质酮（CORT）的血浆水平显著升高。相同的损伤在暴露于乙醚2.5分钟后对激素水平没有影响。将结晶CORT植入MpFC的相同区域，在束缚应激下可使ACTH和CORT的血浆水平显著降低，但同样，对乙醚应激没有影响。MpFC损伤或CORT植入对上午或下午血浆ACTH或CORT水平均无任何一致的影响。MpFC功能的操作与CORT清除率或垂体、下丘脑、海马或杏仁核中皮质类固醇受体密度的变化无关。综上所述，这些发现表明MpFC是糖皮质激素对应激诱导的HPA活动负反馈作用的靶位点，并且这种作用取决于应激的性质。
