Sex steroids and epidermal growth factor in benign prostatic hyperplasia (BPH).
Androgens provide the primary signal for the onset of DNA synthesis and cell division in normal prostate and benign prostatic hyperplasia (BPH). It is possible, however, that androgen mitogenic activity is in part indirect and mediated by peptide growth factors. In LNCaP cell lines, R1881 added to DCC-FCS medium increases DNA, epidermal growth factor (EGF) and EGF receptor (EGFR) levels: the antiandrogen hydroxy-flutamide prevents the increase of the growth factor and increases its receptor. In BPH tissue removed by transvesical prostatectomy, DHT, testosterone, 3 alpha-androstanediol and nuclear androgen receptors (AR) show a positive linear correlation with EGF: treatment with flutamide decreases significantly the EGF production. Androgens, therefore, represent important modulatory factors of prostatic EGF release. Moreover, androgens and EGF downregulate EGFR, which is probably internalized into the cell and degraded by lisosomes: in fact, a negative linear correlation between EGF, nuclear AR and the high- and low-affinity binding of EGFR is observed. These findings support the hypothesis that the growth-promoting effects of androgens in the prostate are in part mediated by peptide growth factors. The inhibitory effect of antiandrogens on prostatic cell proliferation may be the result of the decreased androgenic support and decreased EGF release and expression.
Sciarra
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Institute of V Clinical Medicine, III Endocrinology University of Rome La Sapienza, Italy.
D000368:Aged; D015113:Androstane-3,17-diol / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D013739:Testosterone / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D004815:Epidermal Growth Factor; D066246:ErbB Receptors