Rat P45017α from Testis: Characterization of a Full-Length cDNA Encoding a Unique Steroid Hydroxylase Capable of Catalyzing Both Δ4- and Δ5-Steroid-17,20-Lyase Reactions

A cDNA clone encoding the complete rat 17α-hydroxylase (P45017α) from testis has been identified and sequenced. The deduced amino acid sequence is found to have 69% similarity with human P45017α, 64% similarity with bovine P45017α, and 47% similarity with chicken P45017α. The protein contains 507 amino acids being one amino acid shorter than the human P45017α as the result of a codon being absent at the position of amino acid 139 in the human sequence. The cDNA hybridizes to a single mRNA (∼2.0 kilobases) in rat testis RNA and Southern analysis indicates the presence of a single CYP17 gene in the rat genome. Expression of this cDNA in COS1 cells leads to production of a steroid hydroxylase which is capable of converting both 17α-hydroxypregnenolone and 17α-hydroxyprogesterone into C19 steroids, dehydroepiandrosterone, and androstenedione, respectively. This activity profile is distinct from that of either the human or bovine forms of P45017α which are unable to catalyze 17,20-lyase conversion of Δ4-C21 st...