Ma X M, Levy A, Lightman S L
Department of Medicine, University of Bristol, United Kingdom.
Endocrinology. 1997 Oct;138(10):4351-7. doi: 10.1210/endo.138.10.5446.
The hypothalamic-pituitary-adrenal axis adapts to periods of chronic or repeated stress. We have now investigated whether there is any differential effect of repeated immobilization stress on CRH and arginine vasopressin (AVP) gene transcription in the hypothalamic paraventricular nucleus (PVN), using probes for both intronic and exonic sequences of the AVP and CRH genes. Daily restraint for 13 days had no significant affect on basal corticosterone level, CRH heteronuclear RNA (hnRNA), CRH messenger RNA (mRNA), AVP hnRNA, or AVP mRNA. After the final episode of acute restraint, on day 14, there was a rapid increase in plasma corticosterone and AVP hnRNA level in the parvocellular subdivision of the PVN, a slower increase in AVP mRNA level in the parvocellular subdivision of the PVN, but no significant change in either CRH hnRNA or CRH mRNA in the PVN. The increase in AVP hnRNA and mRNA was specific to the parvocellular PVN, because there was no change in either transcript in the magnocellular cells of this nucleus. This isolated response is in marked contrast to naive rats, which show a predominant CRH hnRNA and mRNA response, and infers that part of the adaptation to repeated stress results from a down-regulation of CRH gene responsiveness with maintenance or even a compensatory increase in the AVP gene response.
下丘脑 - 垂体 - 肾上腺轴会适应慢性或反复应激的时期。我们现在使用抗利尿激素(AVP)和促肾上腺皮质激素释放激素(CRH)基因的内含子和外显子序列探针,研究反复制动应激对下丘脑室旁核(PVN)中CRH和AVP基因转录是否有任何差异影响。连续13天每天进行束缚对基础皮质酮水平、CRH异核RNA(hnRNA)、CRH信使RNA(mRNA)、AVP hnRNA或AVP mRNA均无显著影响。在第14天急性束缚的最后阶段后,PVN小细胞亚群中的血浆皮质酮和AVP hnRNA水平迅速升高,PVN小细胞亚群中的AVP mRNA水平升高较慢,但PVN中的CRH hnRNA或CRH mRNA均无显著变化。AVP hnRNA和mRNA的增加仅限于PVN小细胞,因为该核大细胞中的两种转录本均无变化。这种单独的反应与未经历过应激的大鼠形成鲜明对比,未经历过应激的大鼠显示出主要的CRH hnRNA和mRNA反应,并推断对反复应激的部分适应是由于CRH基因反应性下调,同时AVP基因反应维持甚至代偿性增加所致。