Impact of restriction of placental and fetal growth on expression of 11 beta-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 re striction of placental growth and function (PR), on 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD-1) and 11 beta HSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. Fe tal 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 11 beta HSD-1 mRNA in the fe tal liver increased significantly between 125 days (7.4 +/- 0.8) and 141-14 5 days gestation (27 +/- 5.3). There was also an approximately 2-fold incre ase in the ratio of 11 beta HSD-1 mRNA/18S rRNA expression in the PR group (53.8 +/- 7.9) compared with that in control animals at 141-145 days gestat ion. There was a significant decrease in 11 beta HSD-2 mRNA in fetal adrena ls between 125 days (41.6 +/- 2.4) and 141-145 days (26.7 +/- 1.1) gestatio n, but there was no effect of PR on the expression of adrenal 11 beta HSD-2 mRNA. 11 beta HSD-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 ther e was no effect of PR on the levels of 11 beta HSD-2 mRNA in the fetal kidn ey. In summary, 11 beta HSD-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 11 beta HSD-1 mRNA in the liver o f growth-restricted fetuses in late gestation. This suggests that there is increased hepatic exposure to cortisol in the growth-restricted fetus, whic h may be important in the reprogramming of hepatic physiology that occurs a fter growth restriction in utero.