Takase Yasukazu, Lévesque Marie-Hélène, Luu-The Van, El-Alfy Mohamed, Labrie Fernand, Pelletier Georges
Oncology and Molecular Endocrinology Laboratory, CHUL Research Center, 2705 Laurier Boulevard, Québec, G1V 4G2, Canada.
J Histochem Cytochem. 2006 Aug;54(8):911-21. doi: 10.1369/jhc.6A6927.2006. Epub 2006 May 1.
There is evidence that estrogens can directly modulate human prostate cell activity. It has also been shown that cultured human prostate cancer LNCaP can synthesize the active estrogen estradiol (E2). To elucidate the metabolism of estrogens in the human prostate, we have studied the expression of enzymes involved in the formation and inactivation of estrogens at the cellular level. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 4, 7, and 12, as well as aromatase mRNA and protein expressions, were studied in benign prostatic hyperplasia (BPH) specimens using in situ hybridization and immunohistochemistry. For 17beta-HSD type 4, only in situ hybridization studies were performed. Identical results were obtained with in situ hybridization and immunohistochemistry. All the enzymes studied were shown to be expressed in both epithelial and stromal cells, with the exception of 17beta-HSD types 4 and 7, which were detected only in the epithelial cells. On the basis of our previous results, showing that 3beta-HSD and 17beta-HSD type 5 are expressed in human prostate, and of the present data, it can be concluded that the human prostate expresses all the enzymes involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2. The local biosynthesis of E2 might be involved in the development and/or progression of prostate pathology such as BPH and prostate cancer through modulation of estrogen receptors, which are also expressed in epithelial and stromal cells.
有证据表明雌激素可直接调节人前列腺细胞的活性。研究还表明,培养的人前列腺癌LNCaP细胞能够合成活性雌激素雌二醇(E2)。为阐明雌激素在人前列腺中的代谢情况,我们在细胞水平上研究了参与雌激素生成和失活的酶的表达。利用原位杂交和免疫组织化学技术,对良性前列腺增生(BPH)标本中的1型、2型、4型、7型和12型17β-羟基类固醇脱氢酶(17β-HSD)以及芳香化酶的mRNA和蛋白表达进行了研究。对于4型17β-HSD,仅进行了原位杂交研究。原位杂交和免疫组织化学得到了相同的结果。除4型和7型17β-HSD仅在上皮细胞中检测到外,所有研究的酶在上皮细胞和基质细胞中均有表达。基于我们之前的研究结果(表明3β-HSD和5型17β-HSD在人前列腺中表达)以及目前的数据,可以得出结论,人前列腺表达了所有参与将循环中的脱氢表雄酮(DHEA)转化为E2的酶。E2的局部生物合成可能通过调节同样在上皮细胞和基质细胞中表达的雌激素受体,参与前列腺疾病如BPH和前列腺癌的发生和/或发展。