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Metabolism of dehydroisoandrosterone and androstenedione in human pulmonary endothelial cells in culture
Authors:L Milewich  T S Hendricks  A R Johnson
Abstract:The capacity of endothelial cells from pulmonary arteries and veins to convert dehydroisoandrosterone (3 beta-hydroxy-5-androsten-17-one) and androstenedione to potent, biologically active steroids was investigated. The metabolites of 3H]dehydroisoandrosterone produced in pulmonary artery endothelial cells were androstenedione and 5-androstene-3 beta, 17 beta-diol. The metabolites isolated from incubation of pulmonary arterial cells with 3H]androstenedione were testosterone, 5 alpha-androstane-3,17-dione, 5 alpha-dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one), isoandrosterone (3 beta-hydroxy-5 alpha-androstan-17-one), and androsterone. The products of 3H]androstenedione metabolism in human pulmonary venous cells were the same as those formed in arterial cells, and in addition, 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol were formed. The rates of metabolite formation from 3H]androstenedione in pulmonary arterial and venous endothelial cells were linear with incubation time up to 3 h. These findings suggest that the pulmonary endothelium is an important site for the metabolism of dehydroisoandrosterone and androstenedione in the human lung. Endothelial cells produce the same metabolites as human lung tissue, with the exception of hydroxylated steroids.
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