Nagasaki Shuji, Miki Yasuhiro, Akahira Jun-ichi, Suzuki Takashi, Sasano Hironobu
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ann N Y Acad Sci. 2009 Feb;1155:25-32. doi: 10.1111/j.1749-6632.2008.03682.x.
Estrogen plays a pivotal role in development and progression of human breast carcinoma. Before menopause the main source of estrogen in women is circulating estrogen secreted from the ovary, but following menopause the source changes to the hormone that is converted from circulating adrenal androgens in peripheral tissues. Therefore, adrenal androgens have to be converted to estrogen to stimulate breast carcinoma cells. In these steps, several enzymes such as aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the production of estrogens. The reaction related to 17beta-HSDs activity is one of the last steps of estradiol biosynthesis, and 14 isozymes of 17beta-HSD have been identified at this juncture. The balance of the relative expression levels of 17beta-HSD isozymes in human breast carcinomas is thought to play a pivotal role in supply of estradiol to estrogen receptor positive carcinoma cells. Understanding the character of 17beta-HSD isozymes in human breast carcinoma thus provides important information on the mechanisms of biosynthesis of estradiol in breast carcinoma and for development of a therapeutic agent targeted for inhibition of local estradiol synthesis in breast carcinoma cells. In the present review we summarize the roles played by 17beta-HSDs in human breast carcinoma to obtain a better understanding of the properties of 17beta-HSDs in human breast carcinoma.
雌激素在人类乳腺癌的发生和发展中起着关键作用。绝经前，女性体内雌激素的主要来源是卵巢分泌的循环雌激素，但绝经后，来源转变为外周组织中由循环肾上腺雄激素转化而来的激素。因此，肾上腺雄激素必须转化为雌激素才能刺激乳腺癌细胞。在这些过程中，几种酶如芳香化酶、类固醇硫酸酯酶和17β-羟基类固醇脱氢酶（17β-HSDs）参与雌激素的生成。与17β-HSDs活性相关的反应是雌二醇生物合成的最后步骤之一，此时已鉴定出14种17β-HSD同工酶。17β-HSD同工酶在人类乳腺癌中相对表达水平的平衡被认为在向雌激素受体阳性癌细胞供应雌二醇方面起着关键作用。因此，了解人类乳腺癌中17β-HSD同工酶的特性，可为乳腺癌中雌二醇的生物合成机制以及开发针对抑制乳腺癌细胞局部雌二醇合成的治疗药物提供重要信息。在本综述中，我们总结了17β-HSDs在人类乳腺癌中的作用，以便更好地了解17β-HSDs在人类乳腺癌中的特性。
