Ontogeny of 11 beta-hydroxysteroid dehydrogenase in ovine fetal kidney and lung.
Eleven-beta-hydroxysteroid dehydrogenase (11 beta-HSD) is an enzyme which degrades 11-hydroxycorticosteroids to biologically inactive 11-oxocorticosteroids (cortisone and 11-dehydrocorticosterone). In some tissues, the activity of this enzyme prevents binding of cortisol to mineralocorticoid receptors. The present experiments were designed to test the hypothesis that the fetal kidney contains 11 beta-HSD, that the activity of 11 beta-HSD in fetal kidney increases near term, and that the fetal lung does not contain significant 11 beta-HSD activity. In kidney and lung tissue from 23 fetal sheep ranging in age between 86 and 145 days' gestation, we measured 11 beta-HSD activity. We found significant activity in fetal kidney (14-85% conversion from cortisol to cortisone) but no measurable activity in fetal lung (0-9%). The activity of 11 beta-HSD was significantly related to fetal gestational age (r = 0.76, n = 14). We conclude that 11 beta-HSD activity in the fetal kidney develops as a function of fetal gestational age, and that activity cannot be demonstrated in fetal lung. We speculate 11 beta-HSD in the fetus might function to alter the sensitivity of target organs to glucocorticoids, as well as to mineralocorticoids, and that the absence of activity in the lung allows a high sensitivity of pulmonary tissue to cortisol at the end of gestation.
Wood
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Department of Physiology, University of Florida College of Medicine, Gainesville 32610-0274, USA.
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D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003348:Cortisone / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007668:Kidney / Q000196:embryology* / Q000201:enzymology*; D008168:Lung / Q000196:embryology* / Q000201:enzymology*; D012756:Sheep / Q000196:embryology*
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone