Wan D C, Livett B G
Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
Eur J Pharmacol. 1989 May 11;172(2):107-15. doi: 10.1016/0922-4106(89)90002-3.
The effects of glucocorticoids on the expression of phenylethanolamine N-methyltransferase (PNMT) mRNA and proenkephalin A (ProEnk A) mRNA in cultures of bovine adrenal chromaffin cells were examined. The expression of PNMT mRNA (approx. 1.1 kilobases) was induced in the presence of glucocorticoids. This induction was of high potency with an EC50 in the range of 1-10 nM for dexamethasone, and was blocked by high concentrations of the glucocorticoid antagonist RU-38486. Cortisol, prednisolone and Reichstein substance S (11-deoxy-17-hydroxycorticosterone) were all effective in stimulating PNMT mRNA expression while cortisone, progesterone and beta-estradiol were without effect. These results indicate that the effects are mediated by specific glucocorticoid receptor activation and exhibited a strict structural requirement for the ability of glucocorticoids to induce PNMT mRNA expression. By contrast, glucocorticoids had no significant effect on the expression of ProEnk A mRNA. In summary, this study provides evidence that glucocorticoids act to regulate PNMT (but not ProEnk A) at the transcriptional level. This differential effect of glucocorticoids suggests that different mechanisms govern the expression of mRNAs required for synthesis of the co-stored secretory components, the enkephalins and adrenaline within the chromaffin cells of the adrenal medulla.
研究了糖皮质激素对牛肾上腺嗜铬细胞培养物中苯乙醇胺N-甲基转移酶（PNMT）mRNA和前脑啡肽原A（ProEnk A）mRNA表达的影响。在糖皮质激素存在的情况下，PNMT mRNA（约1.1千碱基）的表达被诱导。这种诱导具有高效能，地塞米松的半数有效浓度（EC50）在1 - 10 nM范围内，并且被高浓度的糖皮质激素拮抗剂RU - 38486阻断。皮质醇、泼尼松龙和 Reichstein物质S（11 - 脱氧 - 17 - 羟皮质酮）均能有效刺激PNMT mRNA表达，而可的松、孕酮和β - 雌二醇则无此作用。这些结果表明，其作用是由特异性糖皮质激素受体激活介导的，并且糖皮质激素诱导PNMT mRNA表达的能力表现出严格的结构要求。相比之下，糖皮质激素对ProEnk A mRNA的表达没有显著影响。总之，本研究提供了证据表明糖皮质激素在转录水平上调节PNMT（而非ProEnk A）。糖皮质激素的这种差异作用表明，不同的机制调控着肾上腺髓质嗜铬细胞中共储存的分泌成分脑啡肽和肾上腺素合成所需的mRNA的表达。
