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循环、局部前列腺和前列腺内雄激素水平之间的相关性。

Correlation between circulatory, local prostatic, and intra-prostatic androgen levels.

机构信息

Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.

出版信息

Prostate. 2011 Jun 15;71(9):909-14. doi: 10.1002/pros.21307. Epub 2010 Dec 6.

Abstract

BACKGROUND

Testosterone is converted to the more potent androgen dihydrotestosterone (DHT) in the prostate. DHT and androgen metabolites are inactivated by uridine diphospho (UDP)-glucuronosyl transferase (UGT) enzymes. Here we have studied the influence of the prostate gland on the systemic levels of DHT. Moreover, genetic variation in androgen metabolizing UGT enzymes and the intra-prostatic levels of glucuronidated DHT metabolites were investigated.

METHODS

We collected peripheral serum, serum from the local prostatic veins and prostatic tissue from 25 patients undergoing radical prostatectomy. The serum and intra-tissular level of different androgen metabolites were determined by immunological assays and gas chromatography-mass spectrometry (GCMS), respectively.

RESULTS

We found a significant positive correlation between the local prostatic serum DHT levels and (a) prostate weight and (b) circulatory serum levels. There were no correlation between in intra-prostatic hormonal levels and local DHT serum levels. The DHT metabolite 3α-diol-17-glucuronide and 3α-diol-3-glucuronide were significantly associated with UGT2B17 deletion and UGT2B15 Asp85Tyr polymorphisms, respectively.

CONCLUSION

These results indicate that local prostatic DHT production has an influence on systemic serum DHT levels. Moreover, our results support the evidence that the prostate is the main DHT producer and that UGTs are important in the intra-prostatic regulation of androgens.

摘要

背景

在前列腺中,睾酮被转化为更有效的雄激素二氢睾酮(DHT)。DHT 和雄激素代谢物通过尿苷二磷酸(UDP)-葡萄糖醛酸基转移酶(UGT)酶失活。在这里,我们研究了前列腺对 DHT 全身水平的影响。此外,还研究了雄激素代谢UGT 酶的遗传变异和前列腺内葡萄糖醛酸化 DHT 代谢物的水平。

方法

我们从 25 例行根治性前列腺切除术的患者中收集外周血清、前列腺局部静脉血清和前列腺组织。通过免疫测定和气相色谱-质谱联用(GCMS)分别测定血清和组织内不同雄激素代谢物的水平。

结果

我们发现局部前列腺血清 DHT 水平与(a)前列腺重量和(b)循环血清水平呈显著正相关。前列腺内激素水平与局部 DHT 血清水平之间无相关性。DHT 代谢物 3α-二醇-17-葡萄糖醛酸苷和 3α-二醇-3-葡萄糖醛酸苷分别与 UGT2B17 缺失和 UGT2B15 Asp85Tyr 多态性显著相关。

结论

这些结果表明,局部前列腺 DHT 生成对全身血清 DHT 水平有影响。此外,我们的结果支持以下证据:前列腺是 DHT 的主要产生部位,UGT 酶在前列腺内雄激素的调节中起重要作用。

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