Modulating effect of estrogen and testosterone on prostatic stromal cell phenotype differentiation induced by noradrenaline and doxazosin

BACKGROUND. Noradrenaline (NA) has been shown to enhance expression of the contractile phenotype of human prostatic stromal cells in tissue culture. T his study examined the possibility that changing levels of sex hormones in elderly men with BPH may modulate the differentiating effect of NA and henc e the efficacy of alpha(1)-adrenoceptor-blocking drugs. METHODS. Confluent, quiescent stromal cell cultures from 6 different patien ts were treated with combinations of 20 mu M NA, 1 mu M doxazosin, 0.1 mu M beta-estradiol, and 0.1 mu M testosterone, over a period of 10 days. Harve sted cells were labelled with fluorescein-conjugated antisera to alpha-smoo th muscle actin and myosin to identify cells of contractile phenotype which were thereafter analyzed flow-cytometrically. RESULTS. NA increased mean immunoexpression of both actin and myosin. Enhan cement of myosin expression was highly significant (P less than or equal to 0.02). This effect was incompletely opposed by doxazosin. Neither estradio l nor testosterone influenced mean expression of contractile filaments and did not significantly enhance or inhibit the effects of NA or doxazosin. Ho wever, both sex hormones exhibited a differentially powerful effect on cell lines from individual patients. The expression of myosin increased by NA w as further elevated by addition of estradiol in four of the cell lines and by testosterone in three. CONCLUSIONS. The data suggest that levels of estrogens and androgens, eithe r alone or in combination, are unlikely to predict the development of obstr uctive symptoms in patients with BPH or their response to doxazosin. Nevert heless, prostatic stromal cells from individual patients may be exceptional ly sensitive to both sex hormones, with enhanced modulation towards a contr actile phenotype. Since alpha- and beta-subtypes of the estrogen receptor a re differentially expressed between the stroma and epithelium of the early fetal prostate, it is likely that interaction between sex hormones and nora drenaline is an important factor in determining the phenotypic composition of prostatic stroma at this early stage of development, and possibly predis position to BPH during later adult life. Prostate 44:111-117, 2000. (C) 200 0 Wiley-Liss, Inc.