Zebrafish cannot convert 11-ketosteroids into 11beta-hydroxysteroids

What is it about?

Zebrafish is a widely used model species to study endocrine functions and for drug screening and toxicicity assessments. We show that zebrafish lacks enzymatic activity to convert inactive 11-oxoglucocorticoids (cortisone, prednisone) to their active 11β-hydroxyglucocorticoids (cortisol, prednisolone). Moreover, due to the lack of 11-oxoreduction in zebrafish, 11-oxoandrogens are not converted to their 11β-hydroxy forms. Thus, the androgen production pathway in zebrafish is characterized by sustained 11-ketotestosterone formation. These findings are of particular significance when using zebrafish as a model to study endocrine functions, stress responses and effects of pharmaceuticals.

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Why is it important?

Human and higher mammals convert the inactive glucocorticoids cortisone and prednisone into their active forms cortisol and prednisolone. Zebrafish is lacking the enzyme 11beta-HSD1 and cannot catalyze this reaction. Furthermore, Zebrafish produces the major fish androgen 11-ketotestosterone as a terminal androgen, which cannot be back converted to the 11-hydroxylated form. Knowing the differences in glucocorticoid and androgen metabolism between fish and human is important to draw correct conclusions when using Zebrafish as a model organism.