Ontogeny of 11 beta-hydroxysteroid dehydrogenase: Activity in the placenta, kidney, colon of fetal rats and rabbits

Mechanisms to regulate closely fetal GC exposure are of considerable import ance, as certain organs (kidney, brain) are adversely affected by excess GC s. 11 beta -Hydroxysteroid dehydrogenase type 2 (11 beta -HSD2) reduces tra nsplacental passage of maternal GCs to the fetus. We hypothesized that 11 b eta -HSD2, if active in fetal kidney and colon, might allow local tissue mo dulation Of GC access during the critical last trimester. We determined the presence, ontogeny and functionality of 11 beta -HSD in the placenta and f etal, neonatal and adult kidney and colon in rats and rabbits and the corti sol:cortisone ratio in human amniotic fluid, which represents fetal urine. There was clear a 11 beta -HSD2 expression in last trimester fetal colon, k idney and placenta in both rats and rabbits. This appeared of functional im portance, since the potency of cortisol on fetal rabbit colonic sodium flux in the Ussing chamber was increased by 11 beta -HSD inhibition. In human a mniotic fluid, we found a decreasing ratio of cortisol:cortisone across the last trimester, suggesting an analogous onset of renal 11 beta -HSD2 activ ity in the human fetal kidney. Local fetal tissue 11 beta -HSD2 may modulat e exposure to the deleterious effects of GCs upon target tissue maturation during sensitive periods of late gestation when fetal GC levels rise to pre pare other organs (lung) for adaptations at birth.