Induction of phenylethanolamine N-methyltransferase mRNA expression by glucocorticoids in cultured bovine adrenal chromaffin cells.
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.
Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
D C
DC
Wan
B G
BG
Livett
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015735:Mifepristone; D015345:Oligonucleotide Probes; D010625:Phenylethanolamine N-Methyltransferase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D013329:Structure-Activity Relationship
D004963:Estrenes; D005938:Glucocorticoids; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015735:Mifepristone; D010625:Phenylethanolamine N-Methyltransferase