11-beta-Hydroxysteroid dehydrogenase of rat lung: enzyme kinetic, oxidase-reductase ratio, electrolyte and trace element dependence.
The modulation of the intracellular glucocorticoidal effect on surfactant synthesis of the fetal lung by the metabolic capacity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) could be an important factor in lung maturation. The kinetic properties of microsomal 11 beta-HSD of the rat lung are characterized with respect to product inhibition, substrate specificity, effect of electrolytes or trace elements, and the dependence of the oxidase reductase (OR) ratio on incubation conditions. With NADP+ product inhibition of the reductase was demonstrated. The most common trace elements and electrolytes exhibited no effect on the activity of 11 beta-HSD. It is shown that the OR ratio was strongly dependent on assay conditions. With optimal assay conditions oxidase activity exceeds reductase activity in adult and fetal rat lung microsomes (OR ratio > 1). Thus, glucocorticoids are mainly metabolized to their inactive forms. The enzyme activity in the adult is about 10 times higher than in the fetal lung. The low enzyme activity in fetal lungs could be the reason why the glucocorticoidal effects on surfactant synthesis are not suppressed despite the predominance of oxidase activity.
Hundertmark
S
S
Department of Obstetrics and Gynecology, Klinikum Steglitz, Freie Universität Berlin, FRG.
Ragosch
V
V
Schein
B
B
Bühler
H
H
Fromm
M
M
Lorenz
U
U
Weitzel
H K
HK
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone