title: Glucocorticoids decrease phenylethanolamine N-methyltransferase mRNA expression in the immature foetal sheep adrenal.
abstract: This study examined the impact of a chronic physiological elevation of plasma cortisol levels on adrenal catecholamine synthetic enzyme and proenkephalin A mRNA expression in foetal sheep. Cortisol (2.5-3. 0 mg.5 ml-1.24 h-1, n=9) or saline (0.9% saline, n=6) was infused into foetal sheep for 7 days between 109 days and 116 days gestation. Foetal plasma cortisol concentrations were higher (P<0.0005) in the cortisol infused foetuses when compared with the saline infused group (43.07+/-4.13 nmol.l-1 vs 1.67+/-0.10 nmol.l-1). There were no differences, however, in the plasma ACTH levels between the two groups. Using Northern blot analysis, adrenal phenylethanolamine N-methyltransferase (PNMT) mRNA expression was found to be reduced (P<0.005) fivefold in the cortisol infused foetuses when compared with the controls, as was the relative area of the adrenal medulla which stained positively with anti-PNMT (28.1+/-2.5% vs 44.8+/-4.8%, P<0.007). No effect of cortisol infusion was observed on adrenal tyrosine hydroxylase mRNA and protein expression or proenkephalin A mRNA expression. We conclude that before birth, adrenaline synthesis may be suppressed by a novel direct, or indirect, inhibitory effect of glucocorticoids on PNMT mRNA expression.
authors.affiliation: Department of Physiology, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Adams
authors.forename: J T
authors.initials: JT
authors.lastname: Ross
authors.forename: T G
authors.initials: TG
authors.lastname: Butler
authors.forename: I C
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D000311:Adrenal Glands / Q000196:embryology / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D004745:Enkephalins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012756:Sheep; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D000324:Adrenocorticotropic Hormone; D014446:Tyrosine 3-Monooxygenase; D010625:Phenylethanolamine N-Methyltransferase; D006854:Hydrocortisone