Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.
Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.
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去势后，肾上腺雄激素可挽救前列腺二氢睾酮的产生和前列腺癌细胞的生长。
DOI：
10.1016/j.mce.2019.02.018
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发表时间：
2019
影响因子：
4.1
通讯作者：
Smith,GaryJ
中科院分区：
文献类型：
--
作者：
Wu,Yue;Tang,Li;Azabdaftari,Gissou;Pop,Elena;Smith,GaryJ
肾上腺雄激素脱氢表雄酮(DHEA)和脱氢表雄酮-硫酸酯(DHEAS)是前列腺癌(PCA)细胞分泌睾酮(T)和双氢睾酮(DHT)的潜在底物，或直接产生DHT。用新鲜的人前列腺组织和体外培养的人前列腺癌细胞系评价了DHEAS和DHEA产生DHT以及类固醇硫酸酯酶(STS)的作用。STS在良性前列腺组织和前列腺癌组织中均有表达。生理浓度的DHEAS在前列腺组织和前列腺癌细胞系中转化为DHT，这是STS依赖的。DHEAS对雄激素受体(AR)的激活和对PCa细胞生长的刺激是STS依赖的。生理浓度的DHEA在体外不能转化为DHTex活体，但能刺激去势小鼠人PCa细胞系VCaP的活瘤生长。提示DHEAS和DHEA的靶向代谢可加强雄激素剥夺治疗。
Adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are potential substrates for intracrine production of testosterone (T) and dihydrotestosterone (DHT), or directly to DHT, by prostate cancer (PCa) cells. Production of DHT from DHEAS and DHEA, and the role of steroid sulfatase (STS), were evaluated ex vivo using fresh human prostate tissue andin vitrousing human PCa cell lines. STS was expressed in benign prostate tissue and PCa tissue. DHEAS at a physiological concentration was converted to DHT in prostate tissue and PCa cell lines, which was STS-dependent. DHEAS activation of androgen receptor (AR) and stimulation of PCa cell growth were STS-dependent. DHEA at a physiological concentration was not converted to DHTex vivoandin vitro, but stimulatedin vivotumor growth of the human PCa cell line, VCaP, in castrated mice. The findings suggest that targeting metabolism of DHEAS and DHEA may enhance androgen deprivation therapy.