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.


CONCLUSIONS
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.
Yang
K
K
Lawson Research Institute, St. Joseph's Hospital, Department of Obstetrics and Gynecology, London, Ontario, Canada.
Shearman
K
K
Asano
H
H
Richardson
B S
BS
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001784:Blood Gas Analysis; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005865:Gestational Age; D006863:Hydrogen-Ion Concentration; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000860:Hypoxia / Q000378:metabolism*; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases