Molecular characterization of the cynomolgus monkey Macaca fascicularis steroidogenic enzymes belonging to the aldo-keto reductase family

Steroidogenic enzymes belonging to the aldo-keto reductase family (AKR) possess highly homologous sequences while having different activities. To gain further knowledge about the function as well as the regulation of these enzymes in the monkey, we have isolated cDNA sequences encoding monkey type 5 17β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and 3α-hydroxysteroid dehydrogenase, and characterized their enzymatic activity and mRNA tissue distribution. Sequence analysis indicates that these enzymes share approximately 94 and 76% amino acid identity with human and mouse homologs, respectively. Monkey type 5 17β-HSD possesses 95.9% amino acid sequence identity with human type 5 17β-HSD. It catalyzes the transformation of 4-androstenedione into testosterone, but it lacks 20α-hydroxysteroid dehydrogenase activity that is present in the human enzyme. This activity seems to be specific to human, since mouse type 5 17β-HSD does not show significant 20α-HSD activity. In addition, monkey and mouse 20α-HSD possess relatively high 20α-, 3α-, and 17β-HSD activities, while their human counterpart is confined to 20α-HSD activity. The monkey 3α-HSD possesses relatively high 3α-, 17β-, and 20α-HSD activities; human type 1 3α-HSD exerts 3α- and 20α-HSD activities; the mouse 3α-HSD displays a unique 3α-HSD activity. Quantification of mRNA expression shows that the monkey 3α-HSD is exclusively expressed in the liver, while the type 5 17β-HSD is predominately found in the kidney, with lower levels observed in the stomach, liver, and colon. Monkey 20α-HSD mRNA is highly expressed in the kidney, stomach, and liver. Our study provides the basis for future investigations on the regulation and function of these enzymes in the monkey.