| Title: | Functional characterization of two 20beta-hydroxysteroid dehydrogenase type 2 homeologs from Xenopus laevis reveals multispecificity |
| Author(s): | Tokarz J; Schmitt SM; Moller G; Brandli AW; Adamski J; |
| Address: | "Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany. Electronic address: janina.tokarz@helmholtz-muenchen.de. Walter Brendel Centre of Experimental Medicine, University Hospital and Ludwig-Maximilians-University Munich, Munich, Germany. Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany. Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Research Unit Molecular Endocrinology and Metabolism, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany; Lehrstuhl fur Experimentelle Genetik, Technische Universitat Munchen, Freising-Weihenstephan, Germany; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore" |
| Journal Title: | J Steroid Biochem Mol Biol |
| DOI: | 10.1016/j.jsbmb.2021.105874 |
| ISSN/ISBN: | 1879-1220 (Electronic) 0960-0760 (Linking) |
| Abstract: | "The African clawed frog, Xenopus laevis, is a versatile model for biomedical research and is largely similar to mammals in terms of organ development, anatomy, physiology, and hormonal signaling mechanisms. Steroid hormones control a variety of processes and their levels are regulated by hydroxysteroid dehydrogenases (HSDs). The subfamily of 20beta-HSD type 2 enzymes currently comprises eight members from teleost fish and mammals. Here, we report the identification of three 20beta-HSD type 2 genes in X. tropicalis and X. laevis and the functional characterization of the two homeologs from X. laevis. X. laevis Hsd20b2.L and Hsd20b2.S showed high sequence identity with known 20beta-HSD type 2 enzymes and mapped to the two subgenomes of the allotetraploid frog genome. Both homeologs are expressed during embryonic development and in adult tissues, with strongest signals in liver, kidney, intestine, and skin. After recombinant expression in human cell lines, both enzymes co-localized with the endoplasmic reticulum and catalyzed the conversion of cortisone to 20beta-dihydrocortisone. Both Hsd20b2.L and Hsd20b2.S catalyzed the 20beta-reduction of further C(21) steroids (17alpha-hydroxyprogesterone, progesterone, 11-deoxycortisol, 11-deoxycorticosterone), while only Hsd20b2.S was able to convert corticosterone and cortisol to their 20beta-reduced metabolites. Estrone was only a poor and androstenedione no substrate for both enzymes. Our results demonstrate multispecificity of 20beta-HSD type 2 enzymes from X. laevis similar to other teleost 20beta-HSD type 2 enzymes. X. laevis 20beta-HSD type 2 enzymes are probably involved in steroid catabolism and in the generation of pheromones for intraspecies communication. A role in oocyte maturation is unlikely" |
| Keywords: | "17-alpha-Hydroxyprogesterone/metabolism Animals Cortisone/metabolism Cortisone Reductase/*genetics/*metabolism Embryo, Nonmammalian Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic HeLa Cells Humans Phylogeny Recombinant P;" |
| Notes: | "MedlineTokarz, Janina Schmitt, Stefan M Moller, Gabriele Brandli, Andre W Adamski, Jerzy eng Research Support, Non-U.S. Gov't England 2021/03/17 J Steroid Biochem Mol Biol. 2021 Jun; 210:105874. doi: 10.1016/j.jsbmb.2021.105874. Epub 2021 Mar 17" |
