Promiscuous 3β–Hydroxysteroid Dehydrogenases: Testosterone 17β–Hydroxysteroid Dehydrogenase Activities of mouse Type I and VI 3β–Hydroxysteroid Dehydrogenases.

3β–Hydroxysteroid dehydrogenase(3β-HSD) activity is essential for the synthesis of all classes of steroid hormones, converting variousΔ5–3β–hydroxysteroids into hormonally activeΔ4–3–ketosteroids in NAD+–dependent reactions. Certain 3β–HSD isoforms have been reported to exhibit additional dehydrogenase character(e.g., 17–hydroxysteroid dehydrogenase/reductase). We have investigated whether mouse type I(adrenal/gonadal) and type VI 3β–HSDs(uterine/embryonic) display significant 17β–HSD–like activity. Nonsteroidogenic HEK 293T cells were transiently transfected with pCMV–based expression vectors containing mouse type I and type VI 3β–HSDs. Transfected cells expressing either mouse type I or type VI 3β–HSD converted testosterone to androstenedione, albeit at rates one-tenth of those of pregnenolone to progesterone in similarly transfected 293T cells. Our findings demonstrate that the mouse 3β–HSD I and VI isoforms can inactivate testosterone within an intact cell milieu. These findings are important not only in establishment of structure-function relationships, but also whenever murine systems are used for developmental/reproductive paradigms associated with human disorders. [ABSTRACT FROM AUTHOR]