抄録
When [4-14C]-5α-dihydrotestosterone was incubated with the homogenate of human epididymis, 5α-androstane-3α, 17β-diol and 5α-androstane-3β, 17β-diol were identified as major metabolites. The ratio of 3α- to 3β-epimer in androstanediol formation was approximately 2.4. 5α-Androstane-3, 17-dione was also identified as a minor metabolite. Among the subcellular fractions, both the human epididymal 3α-and 3β-hydroxysteroid dehydrogenases were localized almost exclusively in the cytosol fraction (105, 000×g supernatant). Both enzymes had optimum pH at 7.5 and optimum temperature at 46°C. NADPH was a more preferable cofactor than NADH for both dehydrogenases. The Michaelis constants (Km) of 3α- and 3β-hydroxysteroid dehydrogenase for 5α-dihydrotestosterone were similar and estimated as 8×10-5M, but the enzymes were unsaturable with the substrate under the conditions investigated, indicating low affinity and high capacity of both dehydrogenases for 5α-dihydrotestosterone.
The human epididymal 5α-reductase revealed a regional difference in activity. The 5α-reductase activity in the most proximal part of the head (ductuli efferentes) was one seventh to one tenth the activity in the remaining part of the epididymis which was constructed of ductus epididymis. Except for this finding, the activity of 5α-reductase was highest in the head, then declined along the course to the tail portion. The 5α-reductase for testosterone was competitively inhibited by Δ4-3-oxosteroids such as progesterone, 20α-dihydroprogesterone, 17α-hydroxyprogesterone, 4-androstenedione, 11-deoxycorticosterone, corticosterone and 11-deoxycortisol, which had inhibition constants (Ki) of 3.3×10--9M, 2.2×10-9M, 1.8×10-8M, 1.3×10-8M, 8.3×10-9M, 1.5×10-7M and 8.7×10-8M, respectively, suggesting the possibility that the 5α-reduction of testosterone is regulated by other Δ4-3-oxosteroids.
