Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha I-adrenergic receptor antagonist

BACKGROUND. Prostatic stromal cells are believed to be a key factor in the pathogenesis of benign prostatic hyperplasia (BPH). The effect of phenyleph rine, an alpha(1)-adrenergic receptor agonist, and doxazosin, an alpha 1-ad renergic receptor-specific antagonist, on the expression of smooth muscle m yosin-heavy-chain isotypes SM-l and SM-2 was tested in an in vitro model of prostatic smooth muscle cells (SMC). METHODS. Primary prostatic stromal cells, grown in SMC-specific medium, wer e treated with 10 mu M of phenylephrine or 1 mu M Of doxazosin or a combina tion of both. SM-2 to SM-1 mRNA ratios and expression of alpha 1-adrenergic receptor subtypes were determined by means of reverse transcriptase polyme rase chain reaction (RT-PCR) techniques. Cell growth was measured by a cell viability assay. RESULTS. SM-1 mRNA and only very low levels of SM-2 mRNA were detected in p rostatic SMC cultures grown for 4 days in a serum-free base medium. After 6 days of treatment, SM-2 expression increased, highest in the doxazosin-tre ated cultures. In comparison to unstimulated cells, a statistically signifi cant 10-fold increase of the SM-2:SM-I ratio was measured in doxazosin-trea ted cultures. Analysis of alpha 1-adrenergic receptor subtype expression re vealed the presence of mRNAs of subtypes Id and Ib mRNAs. Subtype la was no t expressed. Phenylephrine and doxazosin showed no significant effect on ce ll proliferation and on alpha 1d-adrenergic receptor expression. CONCLUSIONS. SMC can differentiate from a proliferative to a contractile ph enotype, which is accompanied by increased expression of isotope 2 of smoot h muscle myosin heavy chain. Our results suggest that doxazosin seems to ha ve a long-term effect on the differentiation of prostatic stromal cells, in dicating that alpha 1-adrenergic receptor antagonists do not act solely on SMC contractility. (C) 1999 Wiley-Liss, Inc.