Luo X, Kiss A, Rabadan-Diehl C, Aguilera G
Section on Endocrine Physiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Endocrinology. 1995 Sep;136(9):3877-83. doi: 10.1210/endo.136.9.7649095.
The effects of adrenalectomy and glucocorticoids on the regulation of corticotropin-releasing hormone (CRH) receptor expression in the hypothalamic paraventricular nucleus (PVN) and pituitary were studied by in situ hybridization in the rat using a complementary RNA probe directed toward the coding region of the type 1 CRH receptor. Eighteen hours after adrenalectomy, CRH receptor messenger RNA (mRNA) expression in the PVN was significantly increased, whereas longer term adrenalectomy (4 and 6 days) had no effect. This transient effect of adrenalectomy was prevented by glucocorticoid replacement. In intact rats, 4 h after immobilization for 1 h or a single ip hypertonic saline injection, CRH receptor mRNA in the PVN markedly increased (P < 0.01), an effect that was unchanged by adrenalectomy (4 or 6 days) or dexamethasone injection (100 micrograms at -14 and 50 micrograms at -1 h) before stress. In the pituitary, CRH receptor mRNA levels decreased transiently after adrenalectomy (-62% after 18 h), returning to basal levels 4 or 6 days after adrenalectomy. The early decrease was prevented by glucocorticoid replacement. In intact rats, dexamethasone (100 micrograms, sc) caused a significant decrease in pituitary CRH receptor mRNA levels 2-10 h after injection, returning to basal levels after 15 h. On the other hand, dexamethasone (5-300 micrograms, sc) had no effect on pituitary CRH receptor mRNA levels 18 h after injection. The data show that although stress stimulation of CRH mRNA in the PVN is glucocorticoid independent, basal levels are likely to be under dual, transcriptional and posttranscriptional, control by glucocorticoids. In the pituitary, changes in hypothalamic CRFs probably play a major role in the control of CRH receptor mRNA levels during manipulations of circulating glucocorticoids levels. In addition, the inability of long term adrenalectomy and glucocorticoid administration to modify pituitary CRH receptor mRNA levels suggests that CRH receptor down-regulation observed under these experimental conditions depends mainly on translational and post-translational events rather than receptor mRNA levels.
采用针对1型促肾上腺皮质激素释放激素（CRH）受体编码区的互补RNA探针，通过原位杂交技术研究了肾上腺切除术和糖皮质激素对大鼠下丘脑室旁核（PVN）和垂体中CRH受体表达调控的影响。肾上腺切除术后18小时，PVN中CRH受体信使核糖核酸（mRNA）表达显著增加，而长期肾上腺切除术（4天和6天）则无影响。肾上腺切除术的这种短暂效应可通过糖皮质激素替代来预防。在完整大鼠中，固定1小时或单次腹腔注射高渗盐水4小时后，PVN中的CRH受体mRNA显著增加（P<0.01），应激前肾上腺切除术（4天或6天）或地塞米松注射（-14小时时100微克，-1小时时50微克）对此效应无影响。在垂体中，肾上腺切除术后CRH受体mRNA水平短暂下降（18小时后下降62%），肾上腺切除术后4天或6天恢复至基础水平。早期下降可通过糖皮质激素替代来预防。在完整大鼠中，地塞米松（100微克，皮下注射）在注射后2 - 10小时导致垂体CRH受体mRNA水平显著下降，15小时后恢复至基础水平。另一方面，地塞米松（5 - 300微克，皮下注射）在注射18小时后对垂体CRH受体mRNA水平无影响。数据表明，尽管PVN中CRH mRNA的应激刺激不依赖糖皮质激素，但基础水平可能受到糖皮质激素的双重控制，即转录和转录后控制。在垂体中，下丘脑促肾上腺皮质激素释放因子（CRFs）的变化可能在循环糖皮质激素水平调控过程中对CRH受体mRNA水平的控制起主要作用。此外，长期肾上腺切除术和糖皮质激素给药无法改变垂体CRH受体mRNA水平，这表明在这些实验条件下观察到的CRH受体下调主要取决于翻译和翻译后事件，而非受体mRNA水平。
