Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue.
Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue.
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DOI：
10.1530/jme-13-0060
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发表时间：
2013
影响因子：
3.5
通讯作者：
Jones JO
中科院分区：
文献类型：
--
作者：
Zhou Y;Otto-Duessel M;He M;Markel S;Synold T;Jones JO
前列腺癌（PC）是一种年龄和雄激素依赖性疾病。奇怪的是，随着年龄的增长，雄激素的全身水平下降，PC的风险增加。虽然全身雄激素水平与PC风险之间没有相关性，但全身雄激素水平并不能反映前列腺组织中雄激素的水平。在转移性PC中，激素治疗期间雄激素生物合成途径的变化导致癌组织中雄激素水平升高，并有助于持续的雄激素受体（AR）信号传导。在正常前列腺组织中可能发生类似的变化，因为雄激素随着年龄的增长而下降，这有助于肿瘤的发生。我们试图确定大鼠前列腺是否能够在低血清睾酮（T）的情况下维持雄激素的功能水平。将大鼠阉割并植入胶囊以达到阉割、正常、亚生理和超生理水平的T。治疗6周后，LC-MS/MS用于定量血清和前列腺组织中T和双氢睾酮（DHT）的水平。QRT-PCR用于定量参与雄激素/AR信号传导轴的基因的表达。尽管血清中T和DHT的水平显著不同，但来自不同T处理组的前列腺组织中的T和DHT浓度非常相似。此外，雄激素调节基因在前列腺中的表达是相似的所有T治疗组，表明大鼠前列腺可以保持功能性水平的雄激素，尽管血清T水平低。低T处理导致雄激素生物合成基因表达的显著改变，这可能与维持功能性雄激素水平有关。
Prostate cancer (PC) is both an age and androgen-dependent disease. Paradoxically, systemic levels of androgens decline with age as the risk of PC rises. While there is no correlation between systemic androgen levels and the risk of PC, systemic androgen levels do not reflect the levels of androgen in prostate tissue. In metastatic PC, changes in the androgen biosynthesis pathway during hormone therapy cause increased levels of androgens in cancer tissue and contribute to continued androgen receptor (AR) signaling. It is possible that similar changes occur in normal prostate tissue as androgens decline with age and that this contributes to tumorigenesis. We sought to determine if the rat prostate is able to maintain functional levels of androgens despite low serum testosterone (T). Rats were castrated and implanted with capsules to achieve castrate, normal, sub- and supra-physiological levels of T. After six weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. QRT-PCR was used to quantify expression of genes involved in the androgen/AR signaling axis. Despite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were very similar. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the rat prostate can maintain a functional level of androgens despite low serum T levels. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining functional androgen levels.