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

肾上腺雄激素在前列腺和雄激素靶组织中起雄激素源的作用。本研究比较了三种人前列腺癌细胞在活培养条件下对肾上腺雄激素、脱氢表雄酮（DHEA）和雄烯二酮的代谢能力。对雄激素非依赖性细胞株PC-3、DU145和雄激素依赖性细胞株LNCaP进行了研究。同时考察了葡萄糖醛酸盐和硫酸酯缀合物的作用。PC-3或DU145有将雄烯二酮转化为脱氢表雄酮或脱氢表雄酮- s的强烈倾向。另一方面，LNCaP能够将脱氢表雄酮转化为雄烯二酮，随后转化为二氢睾酮（DHT）。此外，雄激素在LNCaP中转化为葡萄糖醛酸缀合物，而在PC-3和DU145中则没有。结果，LNCaP中肾上腺前体的代谢转变为雄激素的形成。这可以通过尿苷二磷酸葡萄糖醛酸转移酶（UGT） 2B15的逆转录pcr证实。LNCaP中UGT活性的动力学性质表明DHT是比睾酮更好的前列腺UGT底物。总之，我们的研究结果表明，肾上腺前体库具有促进前列腺细胞调节的潜力。此外，LNCaP中UGT活性的存在可能对胞内环境中的活性雄激素水平有调节作用。

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.