Effects of Hypoxemia on 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 Gene Expression in Preterm Fetal Sheep

Abstract

Objective

To examine the effect of sustained hypoxia on the expression of 11β-hydroxysteroid dehydrogenase (11β-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 11β-HSD1 and 11β-HSD2 mRNA were determined by Northern blot analysis using ovine 11β-HSD types 1 and 2 cDNAs as probes. Levels of 11β-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 11β-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 11β-HSD2 enzyme activity, indicating that changes in 11β-HSD2 mRNA were unlikely carried through to 11β-HSD2 protein. In contrast, levels of 11β-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 11β-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 11β-HSD enzymes, (J Soc Gynecol Invest 1997;4:124–129) Copyright © 1997 by the Society for Gynecologic Investigation.