Tang Wanjin, Norlin Maria
Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):540-6. doi: 10.1016/j.bbrc.2006.03.175. Epub 2006 Apr 4.
The present study reports effects of androgens and estrogens on human CYP7B1 transcription in prostate cancer LNCaP cells. Studies with rodents have suggested a role for the CYP7B1 enzyme in balancing cellular hormone levels important for prostate growth. Little is, however, known about the regulation of human CYP7B1. The current study showed strong suppression of a human CYP7B1 luciferase reporter gene by dihydrotestosterone (DHT) in prostate cancer LNCaP cells. Also, DHT and overexpression of androgen receptor (AR) suppressed CYP7B1 promoter activity and CYP7B1-mediated catalysis in kidney-derived HEK293 cells. Effects on CYP7B1 transcription were observed also by estrogen receptors (ER). The effects appeared different for different estrogens. CYP7B1 was stimulated by synthetic ER agonists but suppressed by 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol in LNCaP cells. Our data indicate an important role for CYP7B1 in balancing prostate hormone levels in human cells. In particular, the data suggest that androgens may control intraprostatic levels of estrogen via regulation of CYP7B1-mediated metabolism.
本研究报告了雄激素和雌激素对前列腺癌LNCaP细胞中人类CYP7B1转录的影响。对啮齿动物的研究表明，CYP7B1酶在平衡对前列腺生长重要的细胞激素水平方面发挥作用。然而，关于人类CYP7B1的调控知之甚少。目前的研究表明，在前列腺癌LNCaP细胞中，双氢睾酮（DHT）对人类CYP7B1荧光素酶报告基因有强烈抑制作用。此外，DHT和雄激素受体（AR）的过表达抑制了肾源性HEK293细胞中CYP7B1启动子活性和CYP7B1介导的催化作用。雌激素受体（ER）也观察到对CYP7B1转录的影响。不同雌激素的影响似乎有所不同。在LNCaP细胞中，CYP7B1受到合成ER激动剂的刺激，但受到17β-雌二醇和5α-雄甾烷-3β,17β-二醇的抑制。我们的数据表明CYP7B1在平衡人类细胞中前列腺激素水平方面发挥重要作用。特别是，数据表明雄激素可能通过调节CYP7B1介导的代谢来控制前列腺内雌激素水平。
