title: Expression of 3alpha- and 3beta-hydroxy steroid dehydrogenase mRNA in COCs and granulosa cells determines Zearalenone biotransformation.
abstract: Zearalenone (ZEA) is a mycoestrogen found in diverse food and feed materials, particularly in corn and small grains. Following ingestion, the parent zearalenone is converted predominantly into alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) by hepatic hydroxy steroid dehydrogenases (HSD). The present study demonstrated by standard RT-PCR the expression of 3alpha- and 3beta-HSD also in porcine cumulus oocyte complexes (COCs) and granulosa cells isolated form cumulus oocyte complexes. Analysis of the rate of bioconversion of zearalenone (ZEA) by the cultured granulose cells showed the extra-hepatic production of both hydroxy metabolites of ZEA with alpha-ZOL being the dominating metabolites as previously observed in incubations with liver microsomes. The endogenous steroids 5alpha-dihydrotestosterone (5alpha-DHT), and progesterone (PGTN), both known substrates for 3alpha-HSD inhibited the conversion of ZEA into alpha-ZOL. In the presence of pregnelonone (PGN), a major substrate for 3beta-HSD only a slight inhibitory effect on the apparent beta-ZOL formation could be observed. In conclusion, these data indicate that both 3alpha- and 3beta-HSDs are expressed in porcine COCs and GCs, whereas the biotransformation experiments confirm the involvement of these enzymes in the extra-hepatic biotransformation of ZEA.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Utrecht, Yalelaan 16, 3584 CM, 3508 TD Utrecht, The Netherlands. Hassanmalekinejad@yahoo.com
authors.forename: H
authors.initials: H
authors.lastname: Malekinejad
authors.forename: H T A
authors.initials: HT
authors.lastname: Van Tol
authors.forename: B
authors.initials: B
authors.lastname: Colenbrander
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004968:Estrogens, Non-Steroidal / Q000493:pharmacokinetics*; D005260:Female; D015870:Gene Expression; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine / Q000502:physiology; D015025:Zearalenone / Q000493:pharmacokinetics*
chemical_list: D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D015025:Zearalenone; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)