Impact of Restriction of Placental and Fetal Growth on Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 and Type 2 Messenger Ribonucleic Acid in the Liver, Kidney, and Adrenal of the Sheep Fetus

We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) and 11βHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. Fetal liver, kidney, and adrenals were collected from normally grown fetuses at 90 days (n = 6), 125 days (n = 6), and 141–145 days (n = 7) and from PR fetuses at 141–145 days (n = 6). Expression of 11βHSD-1 mRNA in the fetal liver increased significantly between 125 days (7.4 ± 0.8) and 141–145 days gestation (27 ± 5.3). There was also an approximately 2-fold increase in the ratio of 11βHSD-1 mRNA/18S rRNA expression in the PR group (53.8 ± 7.9) compared with that in control animals at 141–145 days gestation. There was a significant decrease in 11βHSD-2 mRNA in fetal adrenals between 125 days (41.6 ± 2.4) and 141–145 days (26.7 ± 1.1) gestation, but there was no effect of PR on the expression of adrenal 11βHSD-2 mRNA. 11βHSD-2 mRNA expression in the fetal kidney increased between 90 days (16.8 ± 1.7) and 141–145 days gestation (31.7 ± 4.3), but there was no effect of PR on the levels of 11βHSD-2 mRNA in the fetal kidney. In summary, 11βHSD-2 mRNA is differentially regulated in the fetal adrenal and kidney in the sheep fetus during late gestation. There is also a specific increase in the expression of 11βHSD-1 mRNA in the liver of growth-restricted fetuses in late gestation. This suggests that there is increased hepatic exposure to cortisol in the growth-restricted fetus, which may be important in the reprogramming of hepatic physiology that occurs after growth restriction in utero.