Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta-Hydroxysteroid dehydrogenase type 2
Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta-Hydroxysteroid dehydrogenase type 2
复制标题
DOI：
10.1016/j.mce.2011.10.022
复制
发表时间：
2012-02
影响因子：
4.1
通讯作者：
J. Tokarz;R. Mindnich;William H. J. Norton;G. Möller;M. Angelis;J. Adamski
中科院分区：
文献类型：
--
作者：
J. Tokarz;R. Mindnich;William H. J. Norton;G. Möller;M. Angelis;J. Adamski
羟基类固醇脱氢酶（HSDs）参与类固醇激素的代谢和受体前调节。虽然在哺乳动物中对17β - hsds和11β - hsds进行了广泛的研究，但在鱼类中只发现了很少的同源体。我们发现了一种新的斑马鱼HSD候选者，与17β -HSD 3型和12型密切相关，它在其他物种中有同源物。该酶催化可的松转化为20 -羟基可的松，经LC-MS/MS鉴定。我们将这种新酶命名为20 β - hsd 2型。所有20 β - hsd 2型同源体都位于内质网。斑马鱼20 - β - hsd 2型在胚胎发育期间表达，其表达模式与已知的将皮质醇氧化为可的松的11 - β - hsd 2型相同。在成人组织中，20 β - hsd 2型表现出普遍存在的表达模式，但存在一些轻微的性别差异。与其他代谢c21 -类固醇并主要参与生殖的酶相比，我们认为硬骨鱼的新型2型20 β - hsds是皮质醇分解代谢的重要酶。
Hydroxysteroid dehydrogenases (HSDs) are involved in metabolism and pre-receptor regulation of steroid hormones. While 17beta-HSDs and 11beta-HSDs are extensively studied in mammals, only few orthologs are characterized in fish. We discovered a novel zebrafish HSD candidate closely related to 17beta-HSD types 3 and 12, which has orthologs in other species. The enzyme catalyzes the conversion of cortisone to 20beta-hydroxycortisone identified by LC-MS/MS. We named the new enzyme 20beta-HSD type 2. All 20beta-HSD type 2 orthologs localize in the endoplasmic reticulum. Zebrafish 20beta-HSD type 2 is expressed during embryonic development showing the same expression pattern as 11beta-HSD type 2 known to oxidize cortisol to cortisone. In adult tissues 20beta-HSD type 2 shows a ubiquitous expression pattern with some minor sex-specific differences. In contrast to other enzymes metabolizing C21-steroids and being mostly involved in reproduction we propose that novel type 2 20beta-HSDs in teleost fish are important enzymes in cortisol catabolism.