Opposite effects of glucocorticoid on hepatic 11 beta-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep.
The level of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA in the fetal sheep liver increases dramatically between day 130 and term (term = day 145), but the causal factors remain unknown. The present study was designed to determine the effects of exogenous glucocorticoid on the fetal hepatic 11 beta-HSD gene expression. Dexamethasone (dex; 2 micrograms/min over 15 min every 2 h) or saline was infused into chronically-catheterized fetal sheep at day 130 of gestation for 4 days. At the end of infusion, the lower right lobe of the liver was collected, total cellular RNA extracted and subjected to Northern blot analysis. It was found that the level of the hepatic 11 beta-HSD mRNA in dex-treated fetuses was about four times higher than that in the saline-treated controls. To examine whether changes occur in the response of hepatic 11 beta-HSD gene expression to glucocorticoids in adulthood, we also treated non-pregnant ewes with dex (10 mg/day) for 4 days. By contrast, this treatment regime in adult sheep produced a small but significant decrease in hepatic 11 beta-HSD mRNA levels. We also determined whether age-specific changes in the hepatic level of 11 beta-HSD mRNA following dex treatment were reflected in the level of 11 beta-HSD enzyme activity. Hepatic 11 beta-HSD activity was determined by a standard in vitro conversion assay using cortisol and cortisone as physiological substrates. In both fetal and adult livers, 11-oxoreductase activity (cortisone-->cortisol) was predominant.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Obstetrics and Gynecology, Lawson Research Institute, University of Western Ontario, St Joseph's Health Centre, London, Canada.
K
K
Yang
E T
ET
Berdusco
J R
JR
Challis
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D015152:Blotting, Northern; D003348:Cortisone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis*; D012756:Sheep / Q000196:embryology*
D012333:RNA, Messenger; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone