In the early stage of androgen-sensitive prostate cancer, cancer cells require androgens to grow. Hormone therapy that lowers androgen output or blocks androgen receptor can suppress the growth of this type of prostate cancer. Rutin, a flavonoid derivative of many plants, has numerous pharmacological effects. The objective of this study was to investigate the effect of rutin on androgen biosynthesis in Leydig cells isolated from the testes of pubertal rats. Immature Leydig cells isolated from 35 days-old male Sprague-Dawley rats were cultured in vitro with 0.5-50 μM rutin for 3 hr. Rutin significantly inhibited androgen secretion at 0.5, 5 and 50 μM under basal condition (medium only). At 50 μM, rutin also markedly compromised androgen secretion stimulated by 10 ng/ml luteinising hormone and 10 mM 8-bromoadenosine 3', 5'-cyclic monophosphate. Further analysis demonstrated that rutin compromised the transcript levels of Scarb1, Cyp11a1 and Hsd3b1 and their proteins expression. Rutin directly inhibited rat testicular CYP17A1, HSD17B3 and AKR1C14 activities at 50 μM. Rutin did not alter mitochondrial membrane potential at up to 50 μM. In conclusion, rutin suppresses androgen biosynthesis in Leydig cells through multiple mechanisms, thereby having benefits for the treatment of androgen-sensitive prostate cancer.
Keywords: Leydig cells; androgen metabolism; androgen production; rutin; steroidogenic enzymes.
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