Effect of dutasteride on the expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel density in rat and human prostate tissue.
OBJECTIVE
To evaluate the effects of dutasteride on the expression of angiogenesis markers in rat and human prostates.


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-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression was lower in the dutasteride-treated groups than in the control group, except for HIF-1alpha protein. HIF-1alpha and VEGF expression was similar in the 2.5 mg and 5.0 mg groups. Human prostate tissues demonstrated homogeneous staining of HIF-1alpha 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-1alpha and VEGF in rat prostates is suppressed by dutasteride. However, less than 4 weeks of dutasteride administration does not suppress the expression of HIF-1alpha, 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.
Ku
Ja Hyeon
JH
Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
Shin
Jung Ki
JK
Cho
Min Chul
MC
Myung
Jae Kyung
JK
Moon
Kyung Chul
KC
Paick
Jae-Seung
JS
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001378:Azasteroids / Q000494:pharmacology* / Q000627:therapeutic use; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001835:Body Weight; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000187:drug effects*; D008875:Middle Aged; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009929:Organ Size; D011467:Prostate / Q000098:blood supply* / Q000378:metabolism* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D020728:Transurethral Resection of Prostate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018952:Antigens, CD34; D001378:Azasteroids; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000068538:Dutasteride