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Steroids metabolism and Cross-talk of steroid receptors in Prostatic cancer cells

前列腺癌细胞中类固醇代谢和类固醇受体的串扰

基本信息

批准号：
11671542
负责人：
KOH Eitetsu
金额：
$ 2.43万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Adrenal androgens function as an androgen source within prostate and androgen target tissue. In this study, we compared the ability of three human prostatic cancer cell lines to metabolize the adrenal androgens, dehydroepiandrosterone (DHEA) and androstenedione in living cultured condition. Androgen-independent cell lines PC-3, DU145 and androgen-dependent cell line LNCaP were investigated. The effect of glucuronide and sulfate conjugates was also investigated. There is a strong tendency in PC-3 or DU145 to convert androstenedione to DHEA or DHEA-S reservoir. On the other hand, LNCaP is capable of converting DHEA into androstenedione and subsequently into dihydrotestosterone (DHT). Moreover, androgens were converted into a glucuronide conjugate in LNCaP, but not in PC-3 or DU145. As a result, the metabolism of the adrenal precursor shifted to androgen formation in LNCaP.This could be confirmed by means of reverse transcription-PCR of uridine diphospho-glucuronosyltransferase (UGT) 2B15. Kinetic properties of UGT activity in LNCaP revealed DHT to be a better substrate than testosterone for prostatic UGTs. In conclusion, our findings show that the adrenal precursor pool has the potential to contribute to the regulation of prostatic cells. Moreover, the presence of UGT activities in LNCaP may have a regulatory effect on the active androgen level in the intracellular environment.

肾上腺雄激素在前列腺和雄激素靶组织中作为雄激素源发挥作用。本研究比较了三种人前列腺癌细胞株在活体培养条件下代谢肾上腺雄激素脱氢表雄酮（DHEA）和雄烯二酮的能力。研究了雄激素非依赖性细胞系PC-3、DU 145和雄激素依赖性细胞系LNCaP。还研究了葡糖苷酸和硫酸盐结合物的作用。在PC-3或DU 145中存在将雄烯二酮转化为DHEA或DHEA-S储库的强烈趋势。另一方面，LNCaP能够将DHEA转化为雄烯二酮，随后转化为双氢睾酮（DHT）。此外，雄激素在LNCaP中转化为葡糖苷酸结合物，但在PC-3或DU 145中未转化。尿苷二磷酸葡萄糖醛酸基转移酶（UGT）2B 15的逆转录-PCR证实了LNCaP中肾上腺前体的代谢向雄激素的形成转变。LNCaP中UGT活性的动力学特性显示，对于前列腺UGT，DHT是比睾酮更好的底物。总之，我们的研究结果表明，肾上腺前体池有可能有助于前列腺细胞的调节。此外，LNCaP中UGT活性的存在可能对细胞内环境中的活性雄激素水平具有调节作用。