title: Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta-hydroxysteroid dehydrogenase type 2.
abstract: 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.
authors: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Janina
authors: J
authors: Tokarz
authors: Rebekka
authors: R
authors: Mindnich
authors: William
authors: W
authors: Norton
authors: Gabriele
authors: G
authors: Möller
authors: Martin
authors: M
authors: Hrabé de Angelis
authors: Jerzy
authors: J
authors: Adamski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003348:Cortisone / Q000378:metabolism; D003349:Cortisone Reductase / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D029941:Fish Proteins; D007527:Isoenzymes; D003349:Cortisone Reductase; D003348:Cortisone; D006854:Hydrocortisone