Taxifolin suppresses rat and human testicular androgen biosynthetic enzymes

• Published in: Fitoterapia Vol. 125; pp. 258 - 265
• Main Authors: Ge, Fei, Tian, Erpo, Wang, Li, Li, Xiaoheng, Zhu, Qiqi, Wang, Yiyan, Zhong, Ying, Ge, Ren-Shan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2018; Elsevier Science Ltd
• Subjects: 17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; 17α-hydroxylase/17,20-lyase; 3β-hydroxysteroid dehydrogenase; Androgens; Androgens - biosynthesis; Androstenedione; Animals; Biosynthesis; Cancer; Cells, Cultured; Enzymatic activity; Enzymes; Flavonoids; Flowers & plants; Humans; Hydroxylase; Leydig cells; Leydig Cells - drug effects; Leydig Cells - enzymology; Luteinizing hormone; Male; Pregnenolone; Progesterone; Prostate cancer; Quercetin - analogs & derivatives; Quercetin - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Steroidogenesis; Substrates; Taxifolin; Testis - drug effects; Testis - enzymology; Testosterone; DIOL; P4; P5; 8BR; HSD17B3; TAX; 17α-hydroxylase/17,20-lyase; 3β-hydroxysteroid dehydrogenase; CYP17A1; D4; DHT; 22R; T; HSD3B; Leydig cells; Taxifolin; Steroidogenesis; LH
• ISSN: 0367-326X; 1873-6971
• DOI: 10.1016/j.fitote.2018.01.017

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 100μM taxifolin without (basal) or with 10ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3′,5′-cyclic monophosphate (8BR), and steroid enzyme substrates (20μM): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione. The medium concentrations of 5α-androstane-3α, 17β-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 3β-hydroxysteroid dehydrogenase and 17α-hydroxylase/17, 20-lyase with IC50 values of 14.55±0.013 and 16.75±0.011μM, respectively. Taxifolin also inhibited these two enzyme activities in human testis with IC50 value of about 100μM. 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. [Display omitted]