Functional characterization of two 20 beta-hydroxysteroid dehydrogenase type 2 homeologs from Xenopus laevis reveals multispecificity

Tokarz, Janina; Schmitt, Stefan M.; Moeller, Gabriele; Braendli, Andre W. und Adamski, Jerzy (2021): Functional characterization of two 20 beta-hydroxysteroid dehydrogenase type 2 homeologs from Xenopus laevis reveals multispecificity. In: Journal of Steroid Biochemistry and Molecular Biology, Bd. 210, 105874

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 20 beta-HSD type 2 enzymes currently comprises eight members from teleost fish and mammals. Here, we report the identification of three 20 beta-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 20 beta-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 20 beta-dihydrocortisone. Both Hsd20b2.L and Hsd20b2.S catalyzed the 20 beta-reduction of further C-21 steroids (17 alpha-hydroxyprogesterone, progesterone, 11-deoxycortisol, 11-deoxycorticosterone), while only Hsd20b2.S was able to convert corticosterone and cortisol to their 20 beta-reduced metabolites. Estrone was only a poor and androstenedione no substrate for both enzymes. Our results demonstrate multispecificity of 20 beta-HSD type 2 enzymes from X. laevis similar to other teleost 20 beta-HSD type 2 enzymes. X. laevis 20 beta-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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0960-0760
• Sprache: Englisch