Jacobson L, Sharp F R, Dallman M F
Department of Physiology, University of California, San Francisco 94143-0444.
Endocrinology. 1990 Mar;126(3):1709-19. doi: 10.1210/endo-126-3-1709.
To identify brain sites responding to the removal of corticosterone feedback by adrenalectomy (ADX), rat brains were processed for fos immunocytochemistry 1, 3, and 7 days after ADX, sham-ADX, or no surgery using a polyclonal antiserum to fos residues 132-154. Compared to SHAM, ADX rats exhibited strong fos-like immunoreactivity (FLI) only in the parvocellular neurons of the paraventricular hypothalamic nuclei (PVN) 1, 3, and 7 days after surgery. Replacement with a corticosterone pellet at the time of adrenalectomy (ADX + B) prevented this increase in PVN FLI in three of four rats at 1 day, all rats at 3 days, and two of seven rats 7 days after surgery; 100 micrograms/ml corticosterone in the drinking water for 2 days before perfusion reversed ADX-induced increases in PVN FLI in 7-day ADX rats. Providing 25 micrograms/ml corticosterone in the drinking water to ADX rats for 5 days after surgery did not prevent expression of PVN FLI, even though this dose has been shown to normalize morning basal ACTH levels in ADX rats. Virtually all parvocellular PVN neurons expressing FLI after ADX costained for CRF. Some parvocellular neurons also expressed both fos and vasopressin. In all rats, many brain regions expressed FLI that was not related to adrenalectomy. We conclude that the changes in neuronal FLI correlate with demonstrated changes in neuroendocrine activity after ADX; however, suppression of ADX-induced FLI may require higher replacement levels of corticosterone than inhibition of ADX-induced ACTH secretion.
为了确定因肾上腺切除术(ADX)去除皮质酮反馈而产生反应的脑区,在大鼠接受ADX、假手术或未手术1、3和7天后,使用针对fos残基132 - 154的多克隆抗血清对大鼠脑进行fos免疫细胞化学处理。与假手术组相比,ADX大鼠仅在术后1、3和7天,在下丘脑室旁核(PVN)的小细胞神经元中表现出强烈的fos样免疫反应性(FLI)。在肾上腺切除时植入皮质酮丸剂(ADX + B),在术后1天,4只大鼠中有3只、3天时所有大鼠以及7天时7只大鼠中有2只阻止了PVN中FLI的这种增加;在灌注前2天,给饮用水中添加100微克/毫升皮质酮可逆转7天ADX大鼠中ADX诱导的PVN中FLI的增加。术后给ADX大鼠饮用含25微克/毫升皮质酮的水5天,尽管该剂量已被证明可使ADX大鼠早晨基础促肾上腺皮质激素(ACTH)水平恢复正常,但并未阻止PVN中FLI的表达。实际上,ADX后所有表达FLI的PVN小细胞神经元均与促肾上腺皮质激素释放因子(CRF)共染色。一些小细胞神经元也同时表达fos和血管加压素。在所有大鼠中,许多脑区表达的FLI与肾上腺切除术无关。我们得出结论,神经元FLI的变化与ADX后神经内分泌活动的已证实变化相关;然而,抑制ADX诱导的FLI可能需要比抑制ADX诱导的ACTH分泌更高水平的皮质酮替代。