A premature increase in circulating cortisol suppresses expression of 11 beta hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid in the adrenal of the fetal sheep

We have investigated the effect of intrafetal cortisol administration, befo re the normal prepartum cortisol surge, on the expression of 11 beta hydrox ysteroid dehydrogenase (11 beta HSD) type 2 mRNA in the fetal adrenal, We a lso determined whether increased fetal cortisol concentrations can stimulat e growth of the fetal adrenal gland or increase expression of adrenal stero idogenic enzymes. Cortisol (hydrocortisone succinate: 2.0-3.0 mg in 4.4 ml/ 24 h) was infused into fetal sheep between 109 and 116 days of gestation (c ortisol infused; n 12), and saline was administered to control fetuses (sal ine infused; n = 13) at the same age. There was no effect of cortisol infus ion on the fetal adrenal:body weight ratio (cortisol: 101.7 +/- 5.3 mg/kg; saline: 108.2 +/- 4.3 mg/kg), The ratio of adrenal 11 beta HSD-2 mRNA to 18 S rRNA expression was significantly lower, however, in the cortisol-infused group (0.75 +/- 0.02) compared with the group receiving saline (1.65 +/- 0 ,14). There was no significant effect of intrafetal cortisol on the relativ e abundance of adrenal CYP11A1, CYP17, CYP21A1, and 3 beta HSD mRNA. A prem ature elevation in fetal cortisol therefore resulted in a suppression of ad renal 11 beta HSD-2. Increased intra-adrenal exposure to cortisol at this s tage of gestation is, however, not sufficient to promote adrenal growth or steroidogenic enzyme gene expression.