Li Zhuo, Luu-The Van, Poisson-Paré David, Ouellet Johanne, Li Songyun, Labrie Fernand, Pelletier Georges
Oncology and Molecular Endocrinology Research Center, Laval University Hospital Research Centre (CRCHUL) and Laval University, Quebec City, Quebec, Canada.
Histol Histopathol. 2009 Mar;24(3):273-82. doi: 10.14670/HH-24.273.
It is well documented that human breast is actively involved in the local formation of estrogens. To determine the site(s) of action of enzymes involved in synthesis and metabolism of the most potent estrogen estradiol (E2), we have studied the expression of the following enzymes: 3beta-hydroxysteroid dehydrogenase (3-HSD), 17beta-HSD types 1, 2, 5, 7 and 12, aromatase, steroid sulfatase (STS) and estrogen sulfotransferase (EST) 1E1 at the cellular level in breast. Both in situ hybridization and immunocytochemistry were used for enzyme localization in normal breast tissues. For immunocytochemistry, we used rabbit antibodies, while in situ hybridization studies were performed using (35S)-labeled cRNA probes. Similar results were obtained with both approaches. All the enzymes (3beta-HSD; 17beta-HSD types 1, 5, 7 and 12; aromatase) involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2 as well as STS which converts estradiol sulfate (E2-S) to E2 have been found to be expressed in epithelial cells of acini and/or ducts as well as the stromal cells. Moreover, 17beta-HSD type 2 and EST1E1, two enzymes which inactivate E2, have been also localized in the same cell types. The present results indicate the enzymes which play a role in the synthesis and metabolism of E2 are expressed in both epithelial and stromal cells in human breast.
有充分的文献记载,人类乳腺积极参与雌激素的局部生成。为了确定参与最有效的雌激素雌二醇(E2)合成和代谢的酶的作用位点,我们研究了以下酶的表达:3β-羟基类固醇脱氢酶(3-HSD)、1型、2型、5型、7型和12型17β-羟基类固醇脱氢酶(17β-HSD)、芳香化酶、类固醇硫酸酯酶(STS)和雌激素硫酸转移酶(EST)1E1在乳腺细胞水平的表达。原位杂交和免疫细胞化学均用于正常乳腺组织中酶的定位。对于免疫细胞化学,我们使用兔抗体,而原位杂交研究则使用(35S)标记的cRNA探针进行。两种方法都得到了相似的结果。所有参与将循环脱氢表雄酮(DHEA)转化为E2的酶(3β-HSD;1型、5型、7型和12型17β-HSD;芳香化酶)以及将硫酸雌二醇(E2-S)转化为E2的STS都已发现在腺泡和/或导管的上皮细胞以及基质细胞中表达。此外,使E2失活的两种酶2型17β-HSD和EST1E1也定位于相同的细胞类型中。目前的结果表明,在人类乳腺中,参与E2合成和代谢的酶在上皮细胞和基质细胞中均有表达。