Muscarinic receptor subtype mRNA expression in the human prostate: association with age, pathological diagnosis, prostate size, or potentially interfering medications?

As the prostate abundantly expresses muscarinic receptors and antagonists for such receptors are increasingly used in the treatment of men with voiding function and large prostates, we have explored an association of the mRNA expression of human M 1 , M 2 , M 3 , M 4 , and M 5 receptors in human prostate with patient age, prostate size, prostate-specific antigen level, pathological diagnosis, and concomitant medication. mRNA was isolated from prostate chips of 110 consecutive patients undergoing transurethral resection of the prostate for the treatment of benign prostatic hyperplasia or prostate cancer. Expression of each of the five muscarinic receptor subtype transcripts was assessed by real-time PCR and association with patient age, prostate size, prostate-specific antigen level, pathological diagnosis, and concomitant medication were explored. M 1 and M 4 receptors were the most and least prevalently expressed subtypes in the human prostate, respectively. M 1 receptor mRNA expression was weakly but significantly associated with prostate size ( r = 0.2494, p = 0.0451), but mRNA expression of none of the five subtypes was significantly associated with age, prostate-specific antigen level, pathological diagnosis (benign prostatic hyperplasia vs. prostate cancer), or concomitant medication (5α-reductase inhibitors, α 1 - or β-adrenoceptor antagonists). We conclude that human prostate muscarinic receptor subtype transcripts apparently undergo only a very limited regulation by a variety of physiological, pathophysiological, or treatment factors. In light of the growing use of muscarinic receptor antagonists in men with voiding dysfunction including those with large prostates, the functional role of the weak association between M 1 receptor mRNA expression and prostate size merits further investigation.