十七羟脱氢酶家族研究进展

Progress of Studying on 17Beta-Hydroxysteroid Dehydrogenases

十七羟脱氢酶(17β-HSDs)是一类与固醇类激素代谢直接相关的酶,它们催化雌激素活化的第一步和雄激素降解的最后一步,同时17β-HSDs在脂肪酸和胆固醇代谢中也起着重要作用。十七羟脱氢酶家族包括十五种异构酶,它们在体内各组织中广泛分布。这些异构酶的变异会导致体内雌雄激素水平异常,阻碍脂肪酸和胆固醇代谢,进而诱发乳腺癌和前列腺癌等疾病的发生。根据其在体内参与的代谢途径,可以划分为三类:一是与雌雄激素代谢直接相关的异构酶,包括17β-HSD1、17β-HSD2、17β-HSD5、17β-HSD7和17β-HSD14;二是与胆固醇和脂肪酸代谢等相关的异构酶,包括17β-HSD3、17β-HSD4、17β-HSD8、17β-HSD10和17β-HSD12;三是一些新近发现的酶,包括17β-HSD11、17β-HSD13和17β-HSD15。本文就这些异构酶的细胞定位、组织分布、空间结构、生理功能及与疾病关联等方面的研究进展进行了综述,并指出今后研究重点和发展趋势,以期为相关疾病的预防和治疗提供积极有益的参考。

17beta-hydroxysteroid dehydrogenases （17β-HSDs） are closely related with metabolic of estrogen and androgen, and they participate in the last step of estrogen activation and/or first step of androgen degradation. They are involved in metabolism of fatty acid and cholesterol. There are fifteen members in this family, and they are disturbed in most of tissues. Disorder of these enzymes will induce abnormal of estrogen and androgen level, and disturb synthesis of fatty acid and cholesterol, and further induce some serious dis- eases （breast cancer and prostate cancer）. They can be divided into three types according to their participated pathway： one is proteins which are related with metabolism of estrogen and androgen, including 17β-HSD1, 17β-HSD2, 17β-HSD5, 17β-HSD7 and 17β-HSD14; The second is proteins which participated in metabolism of fatty acid and cholesterol, including 17β-HSD3, 17β-HSD4, 17β-HSD8, 17β-HSD10 and 17β-HSD12; Third is some new discovered enzyme, including 17β-HSD11, 17β-HSD13 and 17β-HSD15. In this paper, their cell locations, tissue distributions, protein three dimensional structures, physiological functions and their correlation with diseases are summarized. Development direction and key points related with 17β-HSDs in the future are proposed, and it will shed light on pre- vention and therapy of such diseases.