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. This study examined the possibility that changing levels of sex hormones in elderly men with BPH may modulate the differentiating effect of NA and hence the efficacy of α1-adrenoceptor-blocking drugs. METHODS Confluent, quiescent stromal cell cultures from 6 different patients were treated with combinations of 20 μM NA, 1 μM doxazosin, 0.1 μM β-estradiol, and 0.1 μM testosterone, over a period of 10 days. Harvested cells were labelled with fluorescein-conjugated antisera to α-smooth 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. Enhancement of myosin expression was highly significant (P ≤ 0.02). This effect was incompletely opposed by doxazosin. Neither estradiol nor testosterone influenced mean expression of contractile filaments and did not significantly enhance or inhibit the effects of NA or doxazosin. However, both sex hormones exhibited a differentially powerful effect on cell lines from individual patients. The expression of myosin increased by NA was 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, either alone or in combination, are unlikely to predict the development of obstructive symptoms in patients with BPH or their response to doxazosin. Nevertheless, prostatic stromal cells from individual patients may be exceptionally sensitive to both sex hormones, with enhanced modulation towards a contractile phenotype. Since α- and β-subtypes of the estrogen receptor are differentially expressed between the stroma and epithelium of the early fetal prostate, it is likely that interaction between sex hormones and noradrenaline is an important factor in determining the phenotypic composition of prostatic stroma at this early stage of development, and possibly predisposition to BPH during later adult life. Prostate 44:111–117, 2000. © 2000 Wiley-Liss, Inc.