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.