Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/S0166-445X(00)00100-4
Title (Primary) Antiestrogenicity of β-naphthoflavone and PAHs in cultured rainbow trout hepatocytes: evidence for a role of the arylhydrocarbon receptor
Author Navas, J.M.; Segner, H.
Source Titel Aquatic Toxicology
Year 2000
Department OEC; COE
Volume 51
Issue 1
Page From 79
Page To 92
Language englisch
Keywords Antiestrogenicity; Vitellogenin; Hepatocytes; Polynuclear aromatic hydrocarbons (PAHs); Arylhydrocarbon receptor; Cytochrome P450 1A
Abstract The aims of the present study were to assess, (1) if polyaromatic hydrocarbons (PAHs) are able to inhibit estradiol-regulated vitellogenin synthesis in fish; and (2) if this antiestrogenic activity is mediated through the binding of PAHs to the arylhydrocarbon receptor (AhR). Cultured liver cells of rainbow trout, Oncorhynchus mykiss, were co-exposed to PAHs and 17β-estradiol (E2), and the resulting effects on induction of AhR-regulated 7-ethoxyresorufin-O-deethylase (EROD) activity and on E2-regulated vitellogenesis were investigated. The following test compounds were compared: the PAH 3-methylcholanthrene (3MC), which is a strong EROD inducer, the PAH anthracene (ANT), which is not an inducer of EROD activity, and the model EROD inducer, β-naphthoflavone (βNF). 3MC and βNF led to significant decreases of E2-triggered hepatocellular VTG synthesis, whereas ANT exerted no antiestrogenic activity. The rank order of the antiestrogenic activity of the test substances agreed with their EROD-inducing potency suggesting that their antiestrogenicity might be mediated through the AhR. Further evidence for this assumption comes from the observation that inhibitors such as α-naphthoflavone which interferes with ligand–AhR binding, and 8-methoxypsoralen (8MP), which prevents binding of the occupied AhR to responsive DNA elements, clearly reduced the antiestrogenic effects of the xenobiotics. Furthermore, from the comparison of estradiol concentrations in media of liver cells exposed to the CYP 1A-inducing agents and in media of control cells it is unlikely that the observed antiestrogenic effects were caused by an enhanced E2 catabolism. In conclusion, the results from this study indicate that, (1) AhR-binding PAHs possess an antiestrogenic activity; and (2) that the antiestrogenic activity is mediated through the AhR.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=7478
Navas, J.M., Segner, H. (2000):
Antiestrogenicity of β-naphthoflavone and PAHs in cultured rainbow trout hepatocytes: evidence for a role of the arylhydrocarbon receptor
Aquat. Toxicol. 51 (1), 79 - 92 10.1016/S0166-445X(00)00100-4