Effects of the 5α-reductase inhibitor dutasteride on rat prostate α1A-adrenergic receptor and its mediated contractility.
OBJECTIVE
To clarify the possible interference of the 5α-reductase inhibitor dutasteride with α-adrenergic blockers, whose action is mainly mediated by α1A-adrenergic receptor.


METHODS
Male rats were divided into dutasteride and vehicle-treated groups. The drug treatment group was treated with oral dutasteride 0.5 mg/kg/d, and the control group received vehicle only for 2 months. After the 2-month treatment, the rats' ventral prostate weight changes and the testosterone and dihydrotestosterone levels in the serum were measured. In vitro organ-bath studies, real-time polymerase chain reaction, and tissue-segment binding were performed to determine the expression of α1A-adrenergic receptors and its mediated contractility.


RESULTS
Dutasteride treatment significantly decreased the rats' ventral prostate weight, increased their testosterone levels, and decreased the dihydrotestosterone levels in their serum. There were no marked changes in the α1A-adrenergic receptor messenger ribonucleic acid expression, relative phenylephrine-induced contractility, or nerve-mediated contractility between the groups. Dutasteride treatment caused no marked changes in the relative binding capacity of α1A-adrenergic receptor, whereas it greatly decreased the total protein expression of this subtype and its mediated maximal contraction in the whole ventral prostate.


CONCLUSIONS
These results suggest that dutasteride does not interfere with α-adrenergic blockers but otherwise has beneficial effects on their actions. Therefore, the long-term administration of the combination of dutasteride with an α-adrenergic blocker might be a better choice for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia.
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. Electronic address: dong@u-fukui.ac.jp.
Dong
D
Wang
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Xinmin
X
Zha
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Keiko
K
Nagase
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Hironobu
H
Akino
Translational Research Center, Organization for Life Science Advancement Programs, University of Fukui, Fukui, Japan.
Ikunobu
I
Muramatsu
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Hideaki
H
Ito
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Osamu
O
Yokoyama
D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D000068538:Dutasteride; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D011467:Prostate / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D018340:Receptors, Adrenergic, alpha-1; D000068538:Dutasteride