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

Abstract

3β–Hydroxysteroid dehydrogenase (3β‐HSD) activity is essential for the synthesis of all classes of steroid hormones, converting various Δ5–3β–hydroxysteroids into hormonally active Δ4–3–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.