Subtypes of alpha1-adrenoceptors in BPH: future prospects for personalized medicine

Abstract

The alpha(1)-adrenoceptors (alpha(1)-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, alpha(1)-AR antagonists are now used as first-line medical treatment for BPH. Three alpha(1)-AR subtypes (alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR) have been identified on the basis of results of pharmacological and molecular cloning studies; however, the precise physiological role of individual alpha(1)-AR subtypes remains elusive. The expression levels of alpha(1)-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 alpha(1)-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 alpha(1)-AR antagonists. Further genomic studies will refine our knowledge of the functions of alpha(1)-AR subtypes, lead to new strategies for the clinical management of BPH and, perhaps, enable personalized treatment of BPH in the future.