ACTIVATION OF PROSTATE SPECIFIC ANTIGEN PRECURSOR

前列腺丝氨酸蛋白酶在前列腺疾病的生物学中具有潜在的重要作用。前列腺特异性抗原（PSA）是丝氨酸蛋白酶组织激肽激酶家族的一员，可能通过切割胰岛素生长因子结合蛋白（IGFBP’s）来调节细胞生长。这是很重要的，特别是因为IGF水平升高的男性患前列腺癌的风险增加了4倍。男性良性前列腺增生（BPH）也有异常的前列腺进行性生长。IGF或其他生长因子是否参与这些过程是一个值得研究的有趣问题。当与精浆预先孵育时，PSA也被证明能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可能在前列腺炎发病机制中发挥潜在作用。因此，我们的假设是，PSA和前列腺的其他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）和最近从前列腺中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.