Retinol-binding protein as a biomarker to assess endocrine-disrupting compounds in the environment

Abstract

Endocrine-disrupting compounds (EDC) are predominantly investigated with respect to their ability to mimic or block estrogenic actions. However, it is well-known that EDC can act as agonists or antagonists of androgen- and estrogen-response systems. For that reason, there is an obvious need for bioassays providing the possibility of detecting (anti-)estrogenic and (anti-)androgenic effects. The retinol-binding protein (RBP) seems to be a useful molecular biomarker for assessing all modes of action of EDC, because it is regulated by sex steroid hormones. This study was conducted to establish RBP as a biomarker for determination of (anti-)estrogenic and (anti-)androgenic effects of EDC using a Xenopus laevis primary hepatocyte culture system. It could be shown that RBP mRNA expression in X. laevis hepatocytes was stimulated by estrogens in a dose-dependent manner whereas a combination of estrogen and androgen or estrogen and anti-estrogen treatment suppressed estrogenic stimulating effects. Androgens testosterone and dihydrotestosterone were able to reduce RBP mRNA expression and the anti-androgen vinclozolin could abolish the mRNA synthesis-suppressing activity of the androgen dihydrotestosterone. These results clearly demonstrated that RBP mRNA expression patterns in Xenopus laevis hepatocytes have different modes of (anti-)estrogenic and (anti-)androgenic action and can be used for examination of suspected EDC. Moreover, water samples from sewage-treatment plant effluents were applied to liver cells and expression levels of RBP and estrogen receptor mRNA (a known estrogenic biomarker) were detected. These samples had high estrogenicity but caused low to moderate induction of RBP mRNA synthesis, leading to the conclusion that RBP levels represent the sum of all possible effects (estrogenic and other effects) of EDC in environmental samples.

Xenopus embryonic epidermis as a mucociliary cellular ecosystem to assess the effect of sex hormones in a non-reproductive context

“…Consistent with this view, in tadpole st 20–38, AR and ESR lowest expression levels occurred at the time of E2 and androgen highest peaks [32]. Regarding rbp4 , our results do not support its use as a marker to distinguish estrogenic and androgenic endocrine disruption in Xenopus laevis [29]. However, based on its expression, rbp4 may be involved in MCE differentiation, in agreement with its role in fish skin patterning [54] and the role of retinoid signalling during ciliogenesis and regeneration of respiratory epithelia [55].…”

Use of microarray technology to assess the time course of liver stress response after confinement exposure in gilthead sea bream (Sparus aurata L.)

“…Also, reduced expression is found in the liver of common dentex ( Dentex dentex ), a very stress susceptible fish of the Sparidae family, when mRNA transcript levels are compared to those found in gilthead sea bream [73]. Furthermore, our results indicate that retinol-binding protein, a known estrogenic biomarker [74,75], was persistently down-regulated over the course of stress confinement. As far as we know, there is no information in fish about the stress-mediated response of retinol-binding protein.…”

Site-specific impacts on gene expression and behavior in fathead minnows (Pimephales promelas) exposed in situ to streams adjacent to sewage treatment plants

“…The most highly up-regulated protein in the liver was retinol binding protein (RBP). RBP up-regulation has been related to exposure to estrogenic compounds in Xenopus laevis [26,27]. Signal transducer and activator of transcription 1 (STAT1) is up-regulated in the gonad.…”