title: Hydroxysteroid dehydrogenases in bovine and porcine granulosa cells convert zearalenone into its hydroxylated metabolites alpha-zearalenol and beta-zearalenol.
abstract: The enzymes 3alpha- and 3beta-hydroxysteroid dehydrogenase (3alpha- and 3beta-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 3alpha-HSD and 3beta-HSD. 3alpha-HSD and 3beta-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 alpha-zearalenol and beta-zearalenol. Corresponding to the apparent expression profile, in porcine granulosa cells predominantly alpha-zearalenol was formed, whereas bovine granulosa cells preferentially converted zearalenone into beta-zearalenol. This is the first report demonstrating the extrahepatic biotransformation of zearalenone in target tissues.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy and Toxicology, Utrecht University, Yalelaan 16, 3508 TD, Utrecht, The Netherlands. Hassanmalekinejad@yahoo.com
authors.forename: H
authors.initials: H
authors.lastname: Malekinejad
authors.forename: B
authors.initials: B
authors.lastname: Colenbrander
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000818:Animals; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000201:enzymology*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D013552:Swine / Q000378:metabolism*; D015025:Zearalenone / Q000378:metabolism*; D015029:Zeranol / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C029659:zearalenol; D015025:Zearalenone; D015029:Zeranol; D006913:Hydroxysteroid Dehydrogenases; C028226:taleranol