Important role of the C-terminal region of pig aldo-keto reductase family 1 member C1 in the NADPH-dependent reduction of steroid hormones.

The NADPH-dependent reduction activities of two paralogous pig AKR1C1s with and without 19 additional amino acid residues in C-terminus were evaluated against steroid hormones including 5alpha-dihydrotestosterone, testosterone, progesterone, androstenedione and 5alpha-androstane-3.17-dione, which act as substrates of the AKR1C1S. Among the hormones, the AKR1C1s exhibited the highest activity against 5alpha-dihydrotestosterone and the lowest activity against testosterone and progesterone. Furthermore, the AKR1C1s showed the largest differential activities against; 5alpha-dihydrotestosterone, but no such change of activities was found against progestrone and testosterone. These results suggest that the C-terminal region of AKR1C1 plays an important effect in the reduction activities of pig AKR1C1. Thus, the differential activities of two AKR1C1 paralogs observed in the present study provide important insights in understanding the molecular evolution.