Sciarra F
Institute of V Clinical Medicine, III Endocrinology University of Rome La Sapienza, Italy.
Ann N Y Acad Sci. 1995 Jun 12;761:66-78. doi: 10.1111/j.1749-6632.1995.tb31370.x.
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.
雄激素是正常前列腺和良性前列腺增生（BPH）中DNA合成和细胞分裂开始的主要信号。然而，雄激素的促有丝分裂活性可能部分是间接的，由肽生长因子介导。在LNCaP细胞系中，添加到去激素小牛血清（DCC-FCS）培养基中的R1881可增加DNA、表皮生长因子（EGF）和EGF受体（EGFR）水平：抗雄激素羟基氟他胺可阻止生长因子的增加并增加其受体。在经膀胱前列腺切除术切除的BPH组织中，双氢睾酮（DHT）、睾酮、3α-雄烷二醇和核雄激素受体（AR）与EGF呈正线性相关：氟他胺治疗可显著降低EGF的产生。因此，雄激素是前列腺EGF释放的重要调节因子。此外，雄激素和EGF下调EGFR，EGFR可能被内化到细胞中并被溶酶体降解：事实上，观察到EGF、核AR与EGFR的高亲和力和低亲和力结合之间呈负线性相关。这些发现支持了以下假设，即雄激素在前列腺中的促生长作用部分由肽生长因子介导。抗雄激素对前列腺细胞增殖的抑制作用可能是雄激素支持减少以及EGF释放和表达降低的结果。
