Author/Editor     Tokarz, Janina; Lintelmann, Jutta; Möller, Gabriele; Adamski, Jerzy
Title     Substrate multispecificity among 20[beta]-hydroxysteroid dehydrogenase type 2 members
Type     članek
Vol. and No.     , št. Vol. 510
Publication year     2020
Volume     str. 1-11
ISSN     1872-8057 - Molecular and cellular endocrinology
Language     eng
Abstract     Steroids regulate many physiological processes. Hydroxysteroid dehydrogenases (HSDs) modulate the levels of steroids in pre- and post-receptor metabolism. The subfamily of 20[beta]-HSD type 2 currently comprises six members from six different species. The zebrafish ortholog converts cortisone to 20[beta]-dihydrocortisone and is involved in the catabolism of the stress hormone cortisol. Here, we elucidated the substrate preferences of all 20[beta]-HSD type 2 enzymes towards a selected panel of steroids. For quantification of the substrates and their respective 20[beta]-reduced products, we first developed and validated a liquid chromatography-mass spectrometry based method. Applying this method to activity assays with recombinantly expressed enzymes, our findings indicate that the 20[beta]-HSD type 2 enzymes catalyze the 20[beta]-reduction of a plethora of steroids of the glucocorticoid biosynthesis pathway. The observed multispecificity among the homologous 20[beta]-HSD type 2 enzymes implies different physiological roles in different species.
Keywords     20beta-reduction
catabolism
cortisone
20beta-redukcija
katabolizem
kortizon