Disrupting actions of bisphenol A and malachite green on growth hormone receptor gene expression and signal transduction in seabream

Abstract

Environmental estrogen could mimic natural estrogens thereby disrupting the endocrine systems of human and animals. The actions of such endocrine disruptors have been studied mainly on reproduction and development. However, estrogen could also affect the somatotropic axis via multiple targets such as growth hormone (GH). In the present study, two endocrine disruptors were chosen to investigate their effects on the expression level and signal transduction of growth hormone receptor (GHR) in fish. Using real-time PCR, it was found that exposure to both the estrogenic (bisphenol A) and anti-estrogenic (malachite green) compounds could attenuate the expression levels of GHR1 and GHR2 in black seabream (Acanthopagrus schlegeli) hepatocytes. The expression level of IGF-I, the downstream effector of GHR activation in the liver, was decreased by bisphenol A but not by malachite green. Luciferase reporter assay of the beta-casein promoter was used to monitor GHR signaling in transfected cells. In the fish liver cell line Hepa-T1, both GHR1 and GHR2 signaling were attenuated by bisphenol A and malachite green. This attenuation could only occur in the presence of estrogen receptor, indicating that these agents probably produce their actions via the estrogen receptor. Results of the present study demonstrated that estrogenic or anti-estrogenic compounds could down-regulate the somatotropic axis in fish by affecting both the gene expression and signaling of GHR. In view of the increasing prevalence of these compounds in the environment, the impact on fish growth and development both in the wild and in aquaculture would be considerable.

Environmental estrogens inhibit mRNA and functional expression of growth hormone receptors as well as growth hormone signaling pathways in vitro in rainbow trout (Oncorhynchus mykiss)

“…EE such βS and NP have been found to bind to the estrogen receptor in mammals and teleosts, albeit with a much lower affinity than E2 (Bonefeld-Jorgensen et al, 2001;Tremblay and Van der Kraak, 1998;Knudsen and Pottinger, 1999;Sumpter and Jobling, 1995), which may explain the observed differences in potency and efficacy. ERα mediated E2 and bisphenol A (BPA) attenuated GH signaling as reflected by reduced GH-induced expression of casein in Hepa-T1 cells cotransfected with seabream GHRs (Jiao and Cheng, 2010). ER dependence of EE action appears conserved from fish to mammals as E2-, NP-, BPA-altered GH expression in rat pituitary GH3 cells also could be blocked by ER an antagonist (Dang et al, 2009).…”

Low dose effects of bisphenol A

“…1A). 73,225 These studies showed effects on liver enzymes and markers of oxidative stress, potential markers of liver function, at or below 10 -9 M; two other in vitro studies found effects of higher doses on similar endpoints. 226,227 In laboratory animals, four studies showed low dose effects on the expression of liver enzymes and hepatic gene expression (Fig.…”

Bisphenol A Exposure During Early Development Induces Sex-Specific Changes in Adult Zebrafish Social Interactions

“…While it was shown to bind to a range of hormone receptors (human: Prasanth et al 2010; fish: Jiao and Cheng 2010), there has been particular interest in BPA binding to estrogen receptors (ER), e.g., ERα, ERβ, and estrogen-related receptor gamma, ERRγ (general vertebrate: Ben-Jonathan and Steinmetz 1998; human: Takayanagi et al 2006; fish: Saili et al 2012; mice: Kundakovic et al 2013; rat: Cao et al 2013;). To explain differences in behavioral responses to BPA exposure by males vs. females, Masuo and Ishido (2011) and Kubo et al (2001) suggest BPA action in the locus ceruleus, especially in males.…”