Effect of dutasteride on the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and microvessel density in rat and human prostate tissue

Abstract

Objective. To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates. Material and methods. Eight-week-old male Sprague–Dawley rats were divided into three groups of six each according to dutasteride dose, including the control group (regular diet), 2.5 mg group (2.5 mg/kg dutasteride) and 5.0 mg group (5.0 mg/kg dutasteride). A total of 41 patients awaiting transurethral resection of the prostate (TURP) were divided into two groups: 20 patients received no medication and 21 received 0.5 mg dutasteride daily for 2–4 weeks until TURP. Results. At 2 weeks, dutasteride effected a significant decrease in body weight and prostate weight compared with the control rat group. Analysis by reverse transcription–polymerase chain reaction and Western blot revealed that hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1α protein. HIF-1α and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1α and VEGF with regard to extent, intensity and intracellular location in both groups. There was no significant difference in microvessel density between the two groups. Conclusions. The expression of HIF-1α and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1α, VEGF and microvessel density in human prostate tissue. Further clinical investigation with dutasteride including a larger, placebo-controlled study is warranted to establish the mechanism and duration of dutasteride.

Key Words::

• Dutasteride
• hypoxia-inducible factor
• prostate
• vascular endothelial growth factor
• vascularity

Acknowledgement

This study was supported by a Research Foundation Grant funded by the Korean Urological Association (KUA-2007-GSK Basic & Translational Research – Paick, Jae-Seung, Seoul National University Hospital).