Expression of alpha1-adrenoceptor subtype mRNA as a predictor of the efficacy of subtype selective alpha1-adrenoceptor antagonists in the management of benign prostatic hyperplasia.
OBJECTIVE
We examined the correlation between the expression of alpha1-adrenoceptor subtype mRNA in the prostate and the clinical efficacy of subtype selective alpha1-adrenoceptor antagonists. We discuss the possibility of individualizing drug therapy in patients with benign prostatic hyperplasia.


METHODS
A total of 33 patients randomized to the tamsulosin group and 28 randomized to the naftopidil group were enrolled in this study. Each group of patients was administered 0.2 mg tamsulosin hydrochloride or 50 mg naftopidil daily for 12 weeks. Four prostate needle biopsy specimens were obtained from the transition zone to examine the expression of alpha-adrenoceptor subtypes. Specimens were stored at -80 C until used for TaqMan quantitative reverse transcriptase-polymerase chain reaction, which was performed after 12 weeks of treatment.


RESULTS
Based on the results of quantitative reverse transcriptase-polymerase chain reaction the tamsulosin and naftopidil groups were grouped into alpha1a-adrenoceptor dominant (22 and 12 patients) and alpha1d-adrenoceptor dominant (11 and 16, respectively) subgroups. The efficacy of tamsulosin hydrochloride and naftopidil differed depending on the dominant expression of the alpha1-adrenoceptor subtype in the prostate. Tamsulosin hydrochloride was more effective in patients with dominant expression of the alpha1a-adrenoceptor subtype, whereas naftopidil was more effective in those with dominant expression of the alpha1d-adrenoceptor subtype.


CONCLUSIONS
The expression level of alpha1-adrenoceptor subtype mRNA in the prostate could be a predictor of the efficacy of subtype selective alpha1-adrenoceptor antagonists in patients with benign prostatic hyperplasia. This result implies that genetic differences are responsible for the diverse responses to these drugs.
Kojima
Yoshiyuki
Y
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ykojima@med.nagoyacu.ac.jp
Sasaki
Shoichi
S
Kubota
Yasue
Y
Hayase
Masa
M
Hayashi
Yutaro
Y
Shinoura
Hitomi
H
Tsujimoto
Gozoh
G
Kohri
Kenjiro
K
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000368:Aged; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011467:Prostate / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis*; D013449:Sulfonamides / Q000627:therapeutic use; D000077409:Tamsulosin; D016896:Treatment Outcome
D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D000077409:Tamsulosin; C064357:naftopidil