Glucocorticoids decrease phenylethanolamine N-methyltransferase mRNA expression in the immature foetal sheep adrenal

This study examined the impact of a chronic physiological elevation of plas ma cortisol levels on adrenal catecholamine synthetic enzyme and proenkepha lin 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 con centrations 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 pheny lethanolamine N-methyltransferase (PNMT) mRNA expression was found to be re duced (P < 0.005) fivefold in the cortisol infused foetuses when compared w ith the controls, as was the relative area of the adrenal medulla which sta ined 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 hydroxylas e mRNA and protein expression or proenkephalin A mRNA expression. We conclu de that before birth, adrenaline synthesis may be suppressed by a novel dir ect, or indirect, inhibitory effect of glucocorticoids on PNMT mRNA express ion.