Taxifolin suppresses rat and human testicular androgen biosynthetic enzymes

Taxifolin is a flavonoid. It has been used as a chemopreventive agent and supplement. It may have some beneficial effects to treat prostate cancer by suppressing androgen production in Leydig cells. The objective of the present study was to study the effects of taxifolin on androgen production of rat Leydig cells isolated from immature testis and some rat and human testosterone biosynthetic enzyme activities. Rat Leydig cells were incubated with 100 mu M taxifolin without (basal) or with 10 ng/ml luteinizing hormone (LH), 10 mM 8-bromoadenosine 3',5'-cyclicmonophosphate (8BR), and steroid enzyme substrates (20 mu M): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione. The medium concentrations of 5 alpha-androstane-3 alpha, 17 beta-diol (DIOL) and testosterone were measured. Taxifolin significantly suppressed basal, LH-stimulated, 8BR-stimulated, pregnenolone-mediated, and progesterone-mediated androgen production by Leydig cells. Further study demonstrated that taxifolin inhibited rat 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase/17, 20-lyase with IC50 values of 14.55 +/- 0.013 and 16.75 +/- 0.011 mu M, respectively. Taxifolin also inhibited these two enzyme activities in human testis with IC50 value of about 100 mu M. Taxifolin was a competitive inhibitor for these two enzymes when steroid substrates were used. In conclusion, taxifolin may have benefits for the treatment of prostate cancer.