A 77-base pair LINE-like sequence elicits androgen-dependent mvdp/akr1-b7 expression in mouse vas deferens, but is dispensable for adrenal expression in rats

Mvdp/akr1-b7 (mouse vas deferens protein/aldo-keto reductase 1-B7) encodes an enzyme responsible for detoxification of a steroidogenesis byproduct. MVDP/AKR1-B7 is expressed in both rat and mouse adrenal cortex under ACTH control, whereas strong androgen-dependent accumulation in the vas deferens is mouse specific. Comparison of the regulatory regions of the two orthologs reveals a strong identity, disrupted by acquisition of a 77-bp LINE-derived sequence in the mouse promoter. Although ACTH responsiveness is observed in both species, the absence of this 77-bp sequence in the rat is associated with changes in transcription initiation sites. Transfection studies demonstrate that the CCAAT/enhancer-binding protein and selective promoter factor 1-binding sites previously shown to be essential for cAMP/ACTH induction in the mouse are consequently dispensable in the rat. Our data support the idea that the most striking change generated by this acquisition is the strong, androgen-dependent, vas deferens expression observed in mouse. 1) In rat vas deferens, rakr1-b7 expression is barely detectable and is not androgen sensitive. 2) Androgen receptor binds efficiently to an androgen response element within the 77-bp mouse-specific element. 3) Its insertion confers androgen sensitiveness to rakr1-b7 regulatory regions in an androgen response element-dependent manner in transient transfections. We propose that this acquired androgen-responsive region may be responsible for vas deferens androgen-regulated gene expression in vivo.