Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.

Stress, the physiological reaction to a stressor, is initiated in teleost fish by hormone cascades along the hypothalamus-pituitary-interrenal (HPI) axis. Cortisol is the major stress hormone and contributes to the appropriate stress response by regulating gene expression after binding to the glucoc...

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Autores principales:	Janina Tokarz, William Norton, Gabriele Möller, Martin Hrabé de Angelis, Jerzy Adamski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3be8f346e85c4ef48e97da41dd630ad9
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spelling	oai:doaj.org-article:3be8f346e85c4ef48e97da41dd630ad92021-11-18T08:00:33ZZebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.1932-620310.1371/journal.pone.0054851https://doaj.org/article/3be8f346e85c4ef48e97da41dd630ad92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23349977/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Stress, the physiological reaction to a stressor, is initiated in teleost fish by hormone cascades along the hypothalamus-pituitary-interrenal (HPI) axis. Cortisol is the major stress hormone and contributes to the appropriate stress response by regulating gene expression after binding to the glucocorticoid receptor. Cortisol is inactivated when 11β-hydroxysteroid dehydrogenase (HSD) type 2 catalyzes its oxidation to cortisone. In zebrafish, Danio rerio, cortisone can be further reduced to 20β-hydroxycortisone. This reaction is catalyzed by 20β-HSD type 2, recently discovered by us. Here, we substantiate the hypothesis that 20β-HSD type 2 is involved in cortisol catabolism and stress response. We found that hsd11b2 and hsd20b2 transcripts were up-regulated upon cortisol treatment. Moreover, a cortisol-independent, short-term physical stressor led to the up-regulation of hsd11b2 and hsd20b2 along with several HPI axis genes. The morpholino-induced knock down of hsd20b2 in zebrafish embryos revealed no developmental phenotype under normal culture conditions, but prominent effects were observed after a cortisol challenge. Reporter gene experiments demonstrated that 20β-hydroxycortisone was not a physiological ligand for the zebrafish glucocorticoid or mineralocorticoid receptor but was excreted into the fish holding water. Our experiments show that 20β-HSD type 2, together with 11β-HSD type 2, represents a short pathway in zebrafish to rapidly inactivate and excrete cortisol. Therefore, 20β-HSD type 2 is an important enzyme in stress response.Janina TokarzWilliam NortonGabriele MöllerMartin Hrabé de AngelisJerzy AdamskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54851 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Janina Tokarz William Norton Gabriele Möller Martin Hrabé de Angelis Jerzy Adamski Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
description	Stress, the physiological reaction to a stressor, is initiated in teleost fish by hormone cascades along the hypothalamus-pituitary-interrenal (HPI) axis. Cortisol is the major stress hormone and contributes to the appropriate stress response by regulating gene expression after binding to the glucocorticoid receptor. Cortisol is inactivated when 11β-hydroxysteroid dehydrogenase (HSD) type 2 catalyzes its oxidation to cortisone. In zebrafish, Danio rerio, cortisone can be further reduced to 20β-hydroxycortisone. This reaction is catalyzed by 20β-HSD type 2, recently discovered by us. Here, we substantiate the hypothesis that 20β-HSD type 2 is involved in cortisol catabolism and stress response. We found that hsd11b2 and hsd20b2 transcripts were up-regulated upon cortisol treatment. Moreover, a cortisol-independent, short-term physical stressor led to the up-regulation of hsd11b2 and hsd20b2 along with several HPI axis genes. The morpholino-induced knock down of hsd20b2 in zebrafish embryos revealed no developmental phenotype under normal culture conditions, but prominent effects were observed after a cortisol challenge. Reporter gene experiments demonstrated that 20β-hydroxycortisone was not a physiological ligand for the zebrafish glucocorticoid or mineralocorticoid receptor but was excreted into the fish holding water. Our experiments show that 20β-HSD type 2, together with 11β-HSD type 2, represents a short pathway in zebrafish to rapidly inactivate and excrete cortisol. Therefore, 20β-HSD type 2 is an important enzyme in stress response.
format	article
author	Janina Tokarz William Norton Gabriele Möller Martin Hrabé de Angelis Jerzy Adamski
author_facet	Janina Tokarz William Norton Gabriele Möller Martin Hrabé de Angelis Jerzy Adamski
author_sort	Janina Tokarz
title	Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
title_short	Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
title_full	Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
title_fullStr	Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
title_full_unstemmed	Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
title_sort	zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/3be8f346e85c4ef48e97da41dd630ad9
work_keys_str_mv	AT janinatokarz zebrafish20bhydroxysteroiddehydrogenasetype2isimportantforglucocorticoidcatabolisminstressresponse AT williamnorton zebrafish20bhydroxysteroiddehydrogenasetype2isimportantforglucocorticoidcatabolisminstressresponse AT gabrielemoller zebrafish20bhydroxysteroiddehydrogenasetype2isimportantforglucocorticoidcatabolisminstressresponse AT martinhrabedeangelis zebrafish20bhydroxysteroiddehydrogenasetype2isimportantforglucocorticoidcatabolisminstressresponse AT jerzyadamski zebrafish20bhydroxysteroiddehydrogenasetype2isimportantforglucocorticoidcatabolisminstressresponse
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Zebrafish 20β-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response.

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