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Metabolism of Androsterone and 5-Androstane-3,17β-Diol in Human Lung Tissue and in Pulmonary Endothelial Cells in Culture^*

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics Gynecology, The University of Texas Health Science Center, Southwestern Medical School Dallas, Texas 75235

Address all correspondence and requests for reprints to: Dr. Leon Milewich, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

The metabolism of [³H]androsterone and [³H] 5-androstane–3,17'3–diol ([³H]3-diol) was studied in slices of Human lung tissue and cultures of human pulmonary artery endothelial cells. Lung tissue metabolized [³H]androsterone (0.25 µM) to 5-androstane-3,17–dione (30.3 pmol 100 mg^-1tissue h^-1,) isoandrosterone (0.7 pmol 100 mg^-1 tissue h^-1), 5-dihydrotestosterone (5-DHT; 0.1 pmol 100 mg^-1 tissue h^-1), 3-diol (0.1 pmol 100 mg^-1 tissue h^-1), and two polar metabolites. Pulmonary arterial endothelial cells produced the same metab-olites of [³H]androsterone (0.083 µM), with the exception of the polar compounds [5-androstane-3,17-dione (1.3 pmol mg^-1 protein h^-1,) isoandrosterone (0.1 pmol mg^-1 protein h^-1), 5-DHT (0.2 pmol mg^-1 protein h^-1,) and 3-diol (0.2 pmol mg^-1 protein h^-1)]. Thus, the principal metabolite of [³H]androsterone in both lung tissue and endothelial cells was 5-androstane-3,17-dione.

Human lung tissue metabolized [³H]3-diol (0.28 µM) to 5-DHT (8.8 pmol 100 mg^-1 tissue h^-1,) androsterone (2.2 pmol 100 mg^-1 tissue h^-1) 5-androstane-3,17-dione (0.8 pmol 100 mg^-1tissue h^-1,) isoandrosterone (0.1 pmol 100 mg^-1 tissue h^-1), and four polar metabolites (0.2 pmol 100 mg^-1 tissue h^-1.) 5-DHT was the principal metabolite of [³H]3-diol within the first hour of incubation, but the concentration of this androgen declined thereafter to 3.6 pmol 100 mg^-1 tissue after 4 h of incubation. This decline was correlated with increased 5-androstane-3,17-dione synthesis (6.7 pmol 100 mg^-1 tissue 4 h^-1). Androsterone formation from [(³H]3-diol, however, was linear with time of incubation for 4 h (8.9 pmol 100 mg^-1 tissue 4 h^-1). The formation of these products demonstrates that the principal 5-reduced-Cig-steroid-metabolizing enzymes in human lung are 3-hydroxysteroid oxidoreductase and 17β3-hydroxysteroid oxido-reductase.

^* This work was supported in part by USPHS Grants AM-27257 and HL-18826.

Received April 9, 1984.

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