Padilla G M, Petrow V, Marts S A, Mukherji S
Prostate. 1985;6(2):129-43. doi: 10.1002/pros.2990060203.
Androgen-responsive cells: To determine if testosterone or dihydrotestosterone is the main trophic hormone of prostatic adenocarcinoma, we have treated Dunning R3327H prostatic adenocarcinoma-bearing rats with 6-methylene progesterone, which blocks conversion of testosterone to dihydrotestosterone. Copenhagen-Fisher rats were treated with steroid (20 mg/Kg daily) immediately following implantation of tumor and thereafter for 117 days. There was a 92% inhibition of growth of tumors and a lesser effect upon prostate and seminal vesicles. Tumor-free body weights remained unchanged. Both treated and untreated tumors had equivalent DNA content on a per weight basis. This result supports the thesis that prostatic adenocarcinoma requires dihydrotestosterone for growth. Androgen-insensitive cells: Advanced prostate cancer does not respond to endocrine therapy but is temporarily controlled by the cytotoxic steroid estramustine. The latter shows significant selective binding to prostatic protein. To develop chemotherapeutic agents that will control androgen-insensitive cells and possess improved selectivity for prostatic protein, we have studied a number of steroids for their ability to displace 3H-labeled estramustine from prostatic cytosolic proteins. Surprisingly, a carbamido substituent at the C17 position was found to confer significant binding affinity for prostatic estramustine-binding protein. Extension of this structural characteristic to the estramustine type of molecule is being studied.
为确定睾酮或双氢睾酮是否为前列腺腺癌的主要营养激素，我们用6-亚甲基孕酮处理了携带Dunning R3327H前列腺腺癌的大鼠，该物质可阻断睾酮向双氢睾酮的转化。在植入肿瘤后，立即给哥本哈根-费希尔大鼠每日注射类固醇（20毫克/千克），并持续117天。肿瘤生长受到92%的抑制，对前列腺和精囊的影响较小。无瘤体重保持不变。处理组和未处理组的肿瘤每单位重量的DNA含量相当。这一结果支持了前列腺腺癌生长需要双氢睾酮这一论点。
晚期前列腺癌对内分泌治疗无反应，但可被细胞毒性类固醇雌莫司汀暂时控制。后者显示出与前列腺蛋白有显著的选择性结合。为开发能控制雄激素不敏感细胞并对前列腺蛋白具有更高选择性的化疗药物，我们研究了多种类固醇从前列腺胞质蛋白中置换3H标记雌莫司汀的能力。令人惊讶的是，发现C17位的氨基甲酰基取代基赋予了对前列腺雌莫司汀结合蛋白显著的结合亲和力。正在研究将这种结构特征扩展到雌莫司汀类分子上。
