Characterization of 11 beta-hydroxysteroid dehydrogenase activity in fetal and adult ovine tissues.
11 Beta-hydroxysteroid dehydrogenase (11 beta-HSD) converts 11-hydroxycorticosteroids to 11-oxocorticosteroids, thereby influencing the availability of bioactive cortisol or corticosterone in target tissues. The activity of this enzyme was investigated in sheep by: (1) measuring relative 11 beta-HSD activities in kidney, liver and placenta, and in various areas of the brain (hypothalamus, hippocampus, and brainstem); (2) characterizing the optimum pH of activities in the tested tissues; (3) investigating the possible effect of gonadal steroids on 11 beta-HSD activity in adult hypothalamus and kidney; and (4) investigating possible developmental changes in activities in the tested tissues. The optimum pH in liver and placenta was pH 9-10, whereas the optimum pH in kidney was pH 7-8. In tissues from adult ewes, 11 beta-HSD activity was highest in liver (84.6 +/- 3.8%) and kidney (49.8 +/- 11.6%), lower but measurable in pituitary (38.8 +/- 3.7%), and near the limit of detection in hypothalamus and hippocampus (2.7 +/- 0.9% and 3.2 +/- 0.8% respectively). Liver, kidney and pituitary from late-gestation fetal sheep contained activities which were similar to those in the adult (76.9 +/- 4.5%, 66.0 +/- 6.7% and 26.3 +/- 3.0% respectively). Activity in the pituitary was not related to fetal gestational age. Placenta also contained measureable 11 beta-HSD activity (21.4 +/- 4.7%). However, no activity was detected in hypothalamus (-1.7 +/- 0.2%), hippocampus (-0.2 +/- 0.6%) or brainstem (-1.0 +/- 0.6%) in late-gestation fetal or neonatal sheep. Enzyme activities in kidney and hypothalamus did not change significantly when the circulating concentrations of ovarian steroids were altered over a 1-3-week period. It is concluded that the ovine kidney, liver and placenta, but not hypothalamus or cerebral cortex, contain 11 beta-HSD activity. In addition, there is no change in 11 beta-HSD activity between late-gestation fetal life and adult life, and the relative activities are not altered by the ovarian steroid milieu.
Kim
E K
EK
Department of Pharmacodynamics, University of Florida College of Pharmacy, Gainesville 32610-0487, USA.
Wood
C E
CE
Keller-Wood
M
M
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D001933:Brain Stem / Q000196:embryology / Q000201:enzymology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006624:Hippocampus / Q000196:embryology / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007031:Hypothalamus / Q000196:embryology / Q000201:enzymology; D007668:Kidney / Q000196:embryology / Q000201:enzymology; D008099:Liver / Q000196:embryology / Q000201:enzymology; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012756:Sheep
D009243:NAD; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases