Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer
Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer
复制标题
DOI：
10.1158/1078-0432.ccr-05-0525
复制
发表时间：
2005-07-01
影响因子：
11.5
通讯作者：
Mohler, JL
中科院分区：
文献类型：
--
作者：
Titus, MA;Schell, MJ;Mohler, JL
目的：前列腺癌在雄激素剥夺治疗期间最终复发，尽管血清雄激素水平达到去势水平。雄激素受体和雄激素受体调节蛋白的表达提示复发性前列腺癌中雄激素受体活化许多团体都追求的配体非依赖性雄激素受体激活的机制，但我们发现高水平的睾丸雄激素在复发性前列腺癌tissue using RIA.Experimental Designs：前列腺标本从36名男子采购保存血流，以防止缺血和冷冻保存立即。研究了18例在雄激素剥夺治疗期间局部复发的男性复发性前列腺癌标本和18例未接受激素治疗的男性雄激素刺激的良性前列腺标本。睾酮和双氢睾酮的组织水平进行了测量，在每个标本使用液相色谱/电喷雾串联质谱。睾酮和双氢睾酮水平进行了比较，与临床变量和treatment received.Results：睾酮水平相似，在复发性前列腺癌（3.75 pmol/g组织）和雄激素刺激的良性前列腺（2.75 pmol/g组织，Wilcoxon双侧，P = 0.30）。与雄激素刺激的良性前列腺（13.7 pmol/g组织; Wilcoxon双侧，P < 0.0001）相比，复发性前列腺癌（1.25 pmol/g组织）中的双氢睾酮水平降低了91%，尽管大多数复发性前列腺癌标本中的双氢睾酮水平足以激活雄激素受体。睾酮或双氢睾酮水平与转移状态、抗雄激素治疗或生存率无关（Wilcoxon秩和，均P > 0.2）。结论：复发性前列腺癌可能具有从肾上腺雄激素或胆固醇生物合成睾丸雄激素的能力。这一令人惊讶的发现表明双氢睾酮的内分泌产生，并应被用于复发性前列腺癌的新治疗。
Purpose: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor-regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA.Experimental Designs: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry.Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received.Results: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P = 0.30). Dihydrotestosterone levels decreased 91 % in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P < 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P > 0.2).Conclusions: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.