Nonrespiratory Functions of the Human Lung: In Vitro Metabolism of Tritium-Labeled Progesterone and Pregnenolone*

In this investigation, the metabolism of [7-3HN]pregnenolone and [7-3HN]progesterone by slices of normal human lung tissue was evaluated. Employing a combination of chromatographic techniques and crystallization to either constant specific activity or constant 3H to 14C ratio, the identity of metabolites was established. The metabolites of radiolabeled pregnenolone identified in incubations of lung tissue were: pro-gesterone (6.3 pmol 100 mg–1 protein h–1), 20α-hydroxy-4-preg-nen-3-one (2.0 pmol 100 mg–1 protein h–1), 5α-pregnane-3,20-dione (16 pmol 100 mg–1 protein h–1), 3β-hydroxy-5a-pregnan-20-one (6.4 pmol 100 mg–1 protein h–1), 5-pregnene-3β6,20α-diol (21 pmol 100 mg–1 protein h–1) 5-pregnene-3β,20β-diol (2.7 pmol 100 mg–1 protein h–1), 7α-hydroxypregnenolone (8.0 pmol 100 mg–1 protein h–1), and 7α-hydroxypregnenolone (0.7 pmol 100 mg–1 protein h–1). The metabolites of radiolabeled progesterone identified were: 5α-pregnane-3,20-dione (260 pmol 100 mg–1 protein h–1), 20α-hydroxy-4-pregnen-3-one (97 pmol 100 mg–1 protein h–1), 20α-hydroxy-4-pregnen-3-one (11 pmol 100 mg–1 protein h–1), 3β-hydroxy-5α-pregnan-20-one (6.0 pmol 100 mg–1 protein h–1), and 20α-hydroxy-5a-pregnan-3-one (0.5 pmol mg–1 protein h–1). 17α-Hydroxy-C21-steroid metabolites or C19-steroid metabolites were not formed in these incubations. Small amounts of steroid conjugates were detected. Therefore, the following C21-steroid-metabolizing enzyme activities were demonstrated in human lung tissue: 3β-hydroxysteroid oxidoreduc-tase-Δ6–4 isomerase; 5α-reductase; 3β-, 20α-, and 20β-hydroxyste-roid oxidoreductases; and 7α- and 7β-hydroxylases. These findings are suggestive that the human lung may be a site of metabolism of pregnenolone as well as of progesterone, the predominant C21 -steroid present in the peripheral circulations of ovulatory women during the luteal phase of the ovarian cycle and of women throughout pregnancy.