Substrate multispecificity among 20ß-hydroxysteroid dehydrogenase type 2 members.
Mol Cell Endocrinol
; 510: 110822, 2020 06 15.
Article
in En
| MEDLINE
| ID: mdl-32315721
ABSTRACT
Steroids regulate many physiological processes. Hydroxysteroid dehydrogenases (HSDs) modulate the levels of steroids in pre- and post-receptor metabolism. The subfamily of 20ß-HSD type 2 currently comprises six members from six different species. The zebrafish ortholog converts cortisone to 20ß-dihydrocortisone and is involved in the catabolism of the stress hormone cortisol. Here, we elucidated the substrate preferences of all 20ß-HSD type 2 enzymes towards a selected panel of steroids. For quantification of the substrates and their respective 20ß-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 20ß-HSD type 2 enzymes catalyze the 20ß-reduction of a plethora of steroids of the glucocorticoid biosynthesis pathway. The observed multispecificity among the homologous 20ß-HSD type 2 enzymes implies different physiological roles in different species.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cortisone Reductase
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell Endocrinol
Year:
2020
Document type:
Article
Publication country:
IE
/
IRELAND
/
IRLANDA