Interaction of endocrine disrupting chemicals, singly and in combination, with estrogen-, androgen-, and corticosteroid-binding sites in rainbow trout (Oncorhynchus mykiss)

Abstract

Contact CEH NORA team at noraceh@ceh.ac.ukThe NERC and CEH trademarks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. AbstractThe ability of chemicals with known endocrine disrupting activity to interact with three major teleost steroid-binding sites was evaluated. Representative alkylphenols and phthalates, the pesticides dieldrin and toxaphene, the mycoestrogen zearalenone and the phytoestrogen genistein were tested for their ability to displace native ligand from putative estradiol receptor (ER), testosterone receptor (TR) and cortisol receptor (CR) from rainbow trout liver and brain. The ER displayed a higher affinity for alkylphenols than for phthalates, but both groups of compounds were 10 4 -2.10 5 times less potent than estradiol in displacing specifically bound

The in vivo effect of combinations of octylphenol, butylbenzylphthalate and estradiol on liver estradiol receptor modulation and induction of zona radiata proteins in rainbow trout: no evidence of synergy

“…This is consistent with our observations on the potency of BBP in displacing estradiol from the trout ER in vitro (Knudsen & Pottinger, 1998). These observations contrast with those of Jobling et al (1995) who showed that BBP was an effective competitor in the trout ER assay, promoted growth in an estradiol sensitive cell line and induced transcriptional activity in a human ER system.…”

“…Caution should be employed in making generalisations from these data. Taken together with the findings of Knudsen and Pottinger (1998), in which a wide range of alkylphenols and phthalates were screened for synergy at the level of receptor binding in the rainbow trout ER assay, it appears that synergy between these chemicals is unlikely to occur in trout. It must be noted that in the present study the chemicals were administered by IP-injection so metabolic transformation which may occur during gill uptake from the water into the body (Barron et al, 1989) is excluded.…”

“…At high concentrations BBP does bind to the trout ER Knudsen and Pottinger, 1998) so it remains a possibility that at higher concentrations than those used in this study, BBP could exert an effect on ER activation. However, given the water solubility (2.7 mg/l; Staples et al, 1997) and whole fish bioconcentration factor (9.4 ; Carr et al, 1997) of BBP there seems little likelihood of sufficiently high concentrations occurring in the environment to result in concentrations in vivo which exceed the dose administered in the current study (50 mg/kg body weight).…”

“…It is reasonable to suggest that BBP will not pose a risk as an endocrine disruptor to fish under environmentally realistic conditions. This situation should also apply to other phthalates since BBP is reported to bind to the ER with a similar affinity (Knudsen and Pottinger, 1998), or higher affinity than these related compounds.…”

“…These proteins are induced by both estradiol, the endogenous piscine estrogen, and estrogenic chemicals, with the induction of zona radiata proteins occurring at lower concentrations of estrogen than are necessary to induce vitellogenin (Arukwe et al, 1997). Alkylphenols and phthalates are both weakly estrogenic when tested in a variety of assay systems (Pelissero et al, 1993;Jobling et al 1995;Soto et al, 1995;Nimrod and Benson, 1996;Knudsen & Pottinger, 1998) and there has been some debate as to whether the relatively low levels of estrogenicity displayed by these compounds may increase when they occur in combination, as they do in the environment. However, in a recent study Knudsen and Pottinger (1998) showed that the degree to which [ 3 H]estradiol was displaced from the trout hepatic estradiol receptor (ER) by competing alkylphenols and phthalates did not increase when the competitors were presented in combination compared to the degree of displacement observed when the compounds were tested singly.…”