ACTIVATION OF PROSTATE SPECIFIC ANTIGEN PRECURSOR

前列腺丝氨酸蛋白酶在前列腺病的生物学中具有潜在的重要作用。前列腺特异性抗原(PSA)是组织激肽释放酶丝氨酸蛋白酶家族的一员，可能通过裂解胰岛素生长因子结合蛋白(IGFBP)来调节细胞生长。这一点意义重大，尤其是因为最近有研究表明，IGF水平升高的男性患前列腺癌的风险增加了4倍。患有良性前列腺增生症(BPH)的男性也有前列腺的异常进行性生长。IGF或其他生长因子是否参与了这些过程，这是一个值得研究的有趣问题。当PSA与精浆预先孵育时，也被证明可以引起平滑肌细胞的缓激肽反应。由于缓激肽刺激炎症反应，PSA在前列腺炎的发病机制中可能有潜在的作用。因此，我们的假设是，PSA和其他前列腺丝氨酸蛋白酶可能参与前列腺疾病的发展，如BPH、前列腺炎和前列腺癌。因此，我们建议研究PSA、HK2(另一种前列腺特异性丝氨酸蛋白酶)和最近从前列腺分离的其他丝氨酸蛋白酶的潜在致病机制。

Serine proteases of the prostate have potentially important roles in the biology of prostatic diseases. Prostate specific antigen (PSA), a member of the tissue kallikrein family of serine proteases, may regulate cellular growth by cleaving insulin growth factor-binding proteins (IGFBP's). This is significant especially since men with elevated IGF levels have recently been shown to have a 4-fold increase risk in the development of prostate cancer. Men with benign prostatic hyperplasia (BPH) also have abnormal progressive growth of the prostate gland. Whether IGF or other growth factors are involved in these processes is an intriguing question worth investigation. PSA has also been shown to elicit a bradykinin response by smooth muscle Cells when pre-incubated with seminal plasma. Because bradykinin stimulates inflammatory response, there may be a potential role of PSA in the pathogenesis of prostatitis. Our hypothesis therefore, is that PSA, and other serine proteases of the prostate, may be involved in the development of prostatic diseases such as BPH, prostatitis, and prostate cancer. We therefore, propose to study the potential pathogenic mechanisms of PSA, hK2 (another prostate specific serine protease) and other serine proteases recently isolated from the prostate.