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  • Title: Effects of the 5α-reductase inhibitor dutasteride on rat prostate α1A-adrenergic receptor and its mediated contractility.
    Author: Wang D, Zha X, Nagase K, Akino H, Muramatsu I, Ito H, Yokoyama O.
    Journal: Urology; 2015 Mar; 85(3):704.e9-14. PubMed ID: 25733305.
    Abstract:
    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. CONCLUSION: 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.
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