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Subtypes of α1-adrenoceptors in BPH: future prospects for personalized medicine

Abstract

The α1-adrenoceptors (α1-ARs) are involved in regulation of prostatic smooth muscle tone, and are a critical mediator of lower urinary tract symptoms and pathophysiology in benign prostatic hyperplasia (BPH). As a result, α1-AR antagonists are now used as first-line medical treatment for BPH. Three α1-AR subtypes (α1a-AR, α1b-AR, α1d-AR) have been identified on the basis of results of pharmacological and molecular cloning studies; however, the precise physiological role of individual α1-AR subtypes remains elusive. The expression levels of α1-AR subtypes in the prostate differ between patients, and individual differences in the genetic background of patients with BPH might be associated with variation in responses to subtype-selective α1-AR antagonists. In addition, single nucleotide polymorphism and microarray-based gene expression profiling studies might provide an opportunity to identify markers that predict clinical response and therapeutic tolerance to α1-AR antagonists. Further genomic studies will refine our knowledge of the functions of α1-AR subtypes, lead to new strategies for the clinical management of BPH and, perhaps, enable personalized treatment of BPH in the future.

Key Points

  • The α1-adrenoceptors (α1-ARs) have a major role in the regulation of prostatic smooth muscle tone, and are critical mediators of lower urinary tract symptoms and pathophysiology in benign prostatic hyperplasia (BPH)

  • Thus, α1-AR antagonists are now often used as first-line medical treatment for patients with BPH-associated lower urinary tract symptoms

  • Studies of α1-ARs have provided clues as to subtype-specific physiological function, and response to α1-AR antagonists

  • Molecular genetic approaches, such as genomics, transcriptomics, proteomics and metabolomics, might provide an opportunity to identify predictive markers of clinical response to α1-AR antagonists, and could perhaps enable personalized treatment of BPH in the future

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Figure 1: Human α1-AR subtype amino-acid sequences.
Figure 2: Possible schema of personalized medicine for patients with BPH.
Figure 3: Structure of the α1a-AR and reported SNP sites.

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Acknowledgements

This work was supported in part by research grants from the Scientific Fund of the Japan Health Science Foundation, Grants-in-Aid 19659416 from the Japanese Ministry of Education, Culture, Science and Technology and the Japanese Foundation for Prostate Research.

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Correspondence to Yoshiyuki Kojima.

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Kojima, Y., Sasaki, S., Hayashi, Y. et al. Subtypes of α1-adrenoceptors in BPH: future prospects for personalized medicine. Nat Rev Urol 6, 44–53 (2009). https://doi.org/10.1038/ncpuro1276

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