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Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs).
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljökemi.
Vise andre og tillknytning
2008 (engelsk)Inngår i: Toxicol Appl Pharmacol, ISSN 0041-008X, Vol. 227, nr 1, s. 68-75Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in many different polymers, resins and substrates. Due to their widespread production and use, their high binding affinity to particles, and their lipophilic properties, several PBDE congeners can bioaccumulate in the environment. As a result, PBDEs and their hydroxylated metabolites (OH-PBDEs) have been detected in humans and various wildlife samples, such as birds, seals, and whales. Furthermore, certain OH-PBDEs and their methoxylated derivatives (MeO-PBDEs) are natural products in the marine environment. Recently, our laboratory focused on the possible effects on steroidogenesis of PBDEs and OH-PBDEs, e.g. in the human adrenocortical carcinoma (H295R) cell line indicating that some OH-PBDEs can significantly influence steroidogenic enzymes like CYP19 (aromatase) and CYP17. In the present study, human placental microsomes have been used to study the possible interaction of twenty two OH-PBDEs and MeO-PBDEs with aromatase, the enzyme that mediates the conversion of androgens into estrogens. All OH-PBDE derivates showed significant inhibition of placental aromatase activity with IC(50) values in the low micromolar range, while the MeO-PBDEs did not have any effect on this enzyme activity. Enzyme kinetics studies indicated that two OH-PBDEs, 5-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (5-OH-BDE47) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47), had a mixed-type inhibition of aromatase activity with apparent K(i)/K(i)' of 7.68/0,02 microM and 5.01/0.04 microM respectively. For comparison, some structurally related compounds, a dihydroxylated polybrominated biphenyl, which is a natural product (2,2'-dihyroxy-3,3',5,5'-tetrabromobiphenyl (2,2'-diOH-BB80)) and its non-bromo derivative were also included in the study. Again inhibition of aromatase activity could be measured, but their potency was significantly less than those observed for the OH-PBDEs. These results show that a wide range of OH-PBDEs have the potential to disturb steroidogenesis and indicate a potential mechanism of action of these brominated flame retardant derivatives as endocrine disruptors in humans and wildlife.

sted, utgiver, år, opplag, sider
2008. Vol. 227, nr 1, s. 68-75
Emneord [en]
Aromatase/*metabolism, Aromatase Inhibitors/*pharmacology, Female, Humans, Hydroxylation, Kinetics, Placenta/*enzymology, Polybrominated Biphenyls/*pharmacology
Identifikatorer
URN: urn:nbn:se:su:diva-14579ISI: 000253222600008PubMedID: 18022659OAI: oai:DiVA.org:su-14579DiVA, id: diva2:181099
Tilgjengelig fra: 2008-10-09 Laget: 2008-10-09 Sist oppdatert: 2011-01-10bibliografisk kontrollert

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