Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish

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Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish. / Weger, Meltem; Diotel, Nicolas; Weger, B. D.; Beil, T.; Zaucker, Andreas; Eachus, H. L.; Oakes, J. A.; do Rego, J. L.; Storbeck, Karl-Heinz; Gut, P.; Strähle, U.; Rastegar, S.; Müller, Ferenc; Krone, Nils.

In: Journal of Neuroendocrinology, Vol. 30, No. 4, e12586, 04.2018.

Research output: Contribution to journalArticlepeer-review

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APA

Weger, M., Diotel, N., Weger, B. D., Beil, T., Zaucker, A., Eachus, H. L., Oakes, J. A., do Rego, J. L., Storbeck, K-H., Gut, P., Strähle, U., Rastegar, S., Müller, F., & Krone, N. (2018). Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish. Journal of Neuroendocrinology, 30(4), [e12586]. https://doi.org/10.1111/jne.12586

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Author

Weger, Meltem ; Diotel, Nicolas ; Weger, B. D. ; Beil, T. ; Zaucker, Andreas ; Eachus, H. L. ; Oakes, J. A. ; do Rego, J. L. ; Storbeck, Karl-Heinz ; Gut, P. ; Strähle, U. ; Rastegar, S. ; Müller, Ferenc ; Krone, Nils. / Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish. In: Journal of Neuroendocrinology. 2018 ; Vol. 30, No. 4.

Bibtex

@article{2360093c44114c2c89238b2a83b738da,
title = "Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish",
abstract = "The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterised. Because zebrafish are increasingly employed in endocrine and stress research, a better characterisation of steroidogenic pathways is required to target specific steps in the biosynthetic pathways. In the present study, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing ferredoxin co-factors (fdx1, fdx1b), during zebrafish development. Our studies showed an early expression of all these genes during embryogenesis. In larvae, expression of cyp11a2, cyp11c1, cyp17a2, cyp21a2, hsd3b1 and fdx1b can be detected in the interrenal gland, which is the zebrafish counterpart of the mammalian adrenal gland, whereas the fdx1 transcript is mainly found in the digestive system. Gene expression studies using quantitative reverse transcriptase-PCR and whole-mount in situ hybridisation in the adult zebrafish brain revealed a wide expression of these genes throughout the encephalon, including neurogenic regions. Using ultra-high-performance liquid chromatography tandem mass spectrometry, we were able to demonstrate the presence of the glucocorticoid cortisol in the adult zebrafish brain. Moreover, we demonstrate de novo biosynthesis of cortisol and the neurosteroid tetrahydrodeoxycorticosterone in the adult zebrafish brain from radiolabelled pregnenolone. Taken together, the present study comprises a comprehensive characterisation of the steroidogenic genes and the fdx co-factors facilitating glucocorticoid biosynthesis in zebrafish. Furthermore, we provide additional evidence of de novo neurosteroid biosynthesising in the brain of adult zebrafish facilitated by enzymes involved in glucocorticoid biosynthesis. Our study provides a valuable source for establishing the zebrafish as a translational model with respect to understanding the roles of the genes for glucocorticoid biosynthesis and fdx co-factors during embryonic development and stress, as well as in brain homeostasis and function.",
keywords = "adult brain, development, ferredoxin, glucocorticoid biosynthesis, neurosteroids, steroids, zebrafish",
author = "Meltem Weger and Nicolas Diotel and Weger, {B. D.} and T. Beil and Andreas Zaucker and Eachus, {H. L.} and Oakes, {J. A.} and {do Rego}, {J. L.} and Karl-Heinz Storbeck and P. Gut and U. Str{\"a}hle and S. Rastegar and Ferenc M{\"u}ller and Nils Krone",
year = "2018",
month = apr,
doi = "10.1111/jne.12586",
language = "English",
volume = "30",
journal = "Journal of Neuroendocrinology",
issn = "0953-8194",
publisher = "Wiley",
number = "4",

}

RIS

TY - JOUR

T1 - Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish

AU - Weger, Meltem

AU - Diotel, Nicolas

AU - Weger, B. D.

AU - Beil, T.

AU - Zaucker, Andreas

AU - Eachus, H. L.

AU - Oakes, J. A.

AU - do Rego, J. L.

AU - Storbeck, Karl-Heinz

AU - Gut, P.

AU - Strähle, U.

AU - Rastegar, S.

AU - Müller, Ferenc

AU - Krone, Nils

PY - 2018/4

Y1 - 2018/4

N2 - The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterised. Because zebrafish are increasingly employed in endocrine and stress research, a better characterisation of steroidogenic pathways is required to target specific steps in the biosynthetic pathways. In the present study, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing ferredoxin co-factors (fdx1, fdx1b), during zebrafish development. Our studies showed an early expression of all these genes during embryogenesis. In larvae, expression of cyp11a2, cyp11c1, cyp17a2, cyp21a2, hsd3b1 and fdx1b can be detected in the interrenal gland, which is the zebrafish counterpart of the mammalian adrenal gland, whereas the fdx1 transcript is mainly found in the digestive system. Gene expression studies using quantitative reverse transcriptase-PCR and whole-mount in situ hybridisation in the adult zebrafish brain revealed a wide expression of these genes throughout the encephalon, including neurogenic regions. Using ultra-high-performance liquid chromatography tandem mass spectrometry, we were able to demonstrate the presence of the glucocorticoid cortisol in the adult zebrafish brain. Moreover, we demonstrate de novo biosynthesis of cortisol and the neurosteroid tetrahydrodeoxycorticosterone in the adult zebrafish brain from radiolabelled pregnenolone. Taken together, the present study comprises a comprehensive characterisation of the steroidogenic genes and the fdx co-factors facilitating glucocorticoid biosynthesis in zebrafish. Furthermore, we provide additional evidence of de novo neurosteroid biosynthesising in the brain of adult zebrafish facilitated by enzymes involved in glucocorticoid biosynthesis. Our study provides a valuable source for establishing the zebrafish as a translational model with respect to understanding the roles of the genes for glucocorticoid biosynthesis and fdx co-factors during embryonic development and stress, as well as in brain homeostasis and function.

AB - The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterised. Because zebrafish are increasingly employed in endocrine and stress research, a better characterisation of steroidogenic pathways is required to target specific steps in the biosynthetic pathways. In the present study, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing ferredoxin co-factors (fdx1, fdx1b), during zebrafish development. Our studies showed an early expression of all these genes during embryogenesis. In larvae, expression of cyp11a2, cyp11c1, cyp17a2, cyp21a2, hsd3b1 and fdx1b can be detected in the interrenal gland, which is the zebrafish counterpart of the mammalian adrenal gland, whereas the fdx1 transcript is mainly found in the digestive system. Gene expression studies using quantitative reverse transcriptase-PCR and whole-mount in situ hybridisation in the adult zebrafish brain revealed a wide expression of these genes throughout the encephalon, including neurogenic regions. Using ultra-high-performance liquid chromatography tandem mass spectrometry, we were able to demonstrate the presence of the glucocorticoid cortisol in the adult zebrafish brain. Moreover, we demonstrate de novo biosynthesis of cortisol and the neurosteroid tetrahydrodeoxycorticosterone in the adult zebrafish brain from radiolabelled pregnenolone. Taken together, the present study comprises a comprehensive characterisation of the steroidogenic genes and the fdx co-factors facilitating glucocorticoid biosynthesis in zebrafish. Furthermore, we provide additional evidence of de novo neurosteroid biosynthesising in the brain of adult zebrafish facilitated by enzymes involved in glucocorticoid biosynthesis. Our study provides a valuable source for establishing the zebrafish as a translational model with respect to understanding the roles of the genes for glucocorticoid biosynthesis and fdx co-factors during embryonic development and stress, as well as in brain homeostasis and function.

KW - adult brain

KW - development

KW - ferredoxin

KW - glucocorticoid biosynthesis

KW - neurosteroids

KW - steroids

KW - zebrafish

UR - http://eprints.whiterose.ac.uk/128240/

U2 - 10.1111/jne.12586

DO - 10.1111/jne.12586

M3 - Article

C2 - 29486070

VL - 30

JO - Journal of Neuroendocrinology

JF - Journal of Neuroendocrinology

SN - 0953-8194

IS - 4

M1 - e12586

ER -