Effects of hypoxemia on 11 beta-hydroxysteroid dehydrogenase types 1 and 2 gene expression in preterm fetal sheep.

OBJECTIVE

To examine the effect of sustained hypoxia on the expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and 2 genes in preterm fetal sheep.

METHODS

Fetal liver and kidney as well as placental tissues were collected at days 111-113 of gestation (term = 145 days) after 8 hours of sustained hypoxemia induced by lowering the maternal inspired oxygen (n = 7) or after 8 hours of normoxia to serve as controls (n = 5). Changes in the levels of 11 beta-HSD1 and 11 beta-HSD2 mRNA were determined by Northern blot analysis using ovine 11 beta-HSD types 1 and 2 cDNAs as probes. Levels of 11 beta-HSD2 activity were determined by a standard radiometric conversion assay.

RESULTS

In hypoxic fetuses, there was a tendency for a decrease (P = .08) in levels of 11 beta-HSD2 mRNA in the kidney. This decrease was correlated significantly with the degree of associated fetal acidemia (P < .01). However, there were no corresponding changes in the level of renal 11 beta-HSD2 enzyme activity, indicating that changes in 11 beta-HSD2 mRNA were unlikely carried through to 11 beta-HSD2 protein. In contrast levels of 11 beta-HSD1 mRNA in the placenta and fetal liver were unchanged after sustained hypoxia.

CONCLUSION

These results demonstrate that fetal hypoxemia-induced acidosis selectively down-regulates 11 beta-HSD2 mRNA expression in the preterm fetal sheep kidney. This may provide a further mechanism whereby fetal acidosis alters developmental processes by regulating the bioavailability of glucocorticoids in specific fetal organs through altered local expression of 11 beta-HSD enzymes.