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Hydroxysteroid Dehydrogenases in Bovine and Porcine Granulosa Cells Convert Zearalenone into its Hydroxylated Metabolites α-Zearalenol and β-Zearalenol

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Abstract

The enzymes 3α- and 3β-hydroxysteroid dehydrogenase (3α- and 3β-HSD) play a pivotal role in synthesis of various steroid hormones including oestradiol and testosterone. The structure of the mycotoxin zearalenone resembles many characteristics of steroids and binds to oestrogen receptors as an agonist. Consequently, it is suggested that zearalenone is also a substrate for 3α-HSD and 3β-HSD. 3α-HSD and 3β-HSD isoforms are expressed in the liver and kidney but also in many steroidogenic tissues. It was the aim of the present study to demonstrate the presence of these enzymes in granulosa cells, which were obtained from bovine and porcine ovaries, and to investigate whether zearalenone is a substrate for these enzymes. The results show a species-specific expression pattern in the granulosa cells of both species. Moreover, it was demonstrated that zearalenone when added to the culture medium, is converted into α-zearalenol and β-zearalenol. Corresponding to the apparent expression profile, in porcine granulosa cells predominantly α-zearalenol was formed, whereas bovine granulosa cells preferentially converted zearalenone into β-zearalenol. This is the first report demonstrating the extrahepatic biotransformation of zearalenone in target tissues.

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Abbreviations

5α-DHT:

5α-dihydroxytestosterone

DMEM:

Dulbecco's modified Eagle medium

GC:

granulosa cell

HSD:

hydroxysteroid dehydrogenase

PGN:

pregnenolone

ZEA:

zearalenone

α-ZOL:

α-zearalenol

β-ZOL:

β-zearalenol

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Authors and Affiliations

  1. Department of Veterinary Pharmacology, Pharmacy and Toxicology, Utrecht University, Yalelaan 16, 3508 TD, Utrecht, The Netherlands

    H. Malekinejad & J. Fink-Gremmels

  2. Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, 3508 TD, Utrecht, The Netherlands

    B. Colenbrander

Authors
  1. H. Malekinejad
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  2. B. Colenbrander
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  3. J. Fink-Gremmels
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Correspondence to H. Malekinejad.

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Malekinejad, H., Colenbrander, B. & Fink-Gremmels, J. Hydroxysteroid Dehydrogenases in Bovine and Porcine Granulosa Cells Convert Zearalenone into its Hydroxylated Metabolites α-Zearalenol and β-Zearalenol. Vet Res Commun 30, 445–453 (2006). https://doi.org/10.1007/s11259-006-3325-1

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  • DOI: https://doi.org/10.1007/s11259-006-3325-1

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