Molecular Mechanisms of Action of BPA

Abstract

Bisphenol A (BPA) exposure has been associated with serious endocrine-disrupting effects in humans and wildlife. Toxicological and epidemiological studies evidenced that BPA increases body mass index and disrupts normal cardiovascular physiology by interfering with endogenous hormones in rodents, nonhuman primates, and cell culture test systems. The BPA concentration derived from these experiments were used by government regulatory agencies to determine the safe exposure levels of BPA in humans. However, accumulating literature in vivo and in vitro indicate that at concentrations lower than that reported in toxicological studies, BPA could elicit a different endocrine-disrupting capacity. To further complicate this picture, BPA effects rely on several and diverse mechanisms that converge upon endocrine and reproductive systems. If all or just few of these mechanisms concur to the endocrine-disrupting potential of low doses of BPA is at present still unclear. Thus, taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of BPA on endocrine system.

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

“…On the basis of the results of our study, it might be suspected that dose related BPA exposure changes the normal pattern of hepatic www.fhc.viamedica.pl innervation, which could disturb blood and bile flow in the portal area and microcirculation within hepatic sinusoids. So far, BPA is considered to be an endocrine disrupting compound which reacts with nuclear estrogen receptor [4]. Moreover, it has also been described that BPA could react with membrane epithelial growth factor receptor (EGFR) and via ERK1/2 and AKT signaling pathways.…”

“…It is significantly (1000-2000-fold) weaker than 17b estradiol, but acts similarly to estrogens causing a migration of the cytoplasmic receptor domain and activation of the estrogen nuclear receptor [4]. Plastic or polymer products with a BPA component were originally deemed to be safe, since they exhibit low concentrations of BPA.…”

Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

“…The three high affinity BPA receptors, ERRγ, GPR30, and ERs, were very weakly expressed in the maturation-stage ameloblasts. They are mainly detected in proliferating epithelial and mesenchymal precursor cells of the loop, especially the ERRγ, which is the highest affinity receptor for BPA (Okada et al, 2008; Acconcia et al, 2015). The ERRγ is the in vivo receptor of BPA involved in the mineralization process of otoliths in zebrafish (Tohmé et al, 2014).…”

“…It may therefore constitute a marker of exposure to pollutants that disrupt amelogenesis. The mechanism of action of BPA is still unclear but seem to modulate directly or indirectly the activity of multiple receptors (Acconcia et al, 2015). Among them, BPA has been shown to bind the estrogen receptors (ERα and ERβ) (Delfosse et al, 2012), GPR30 (or GPER) (Pupo et al, 2012) and ERRγ with a high affinity (Liu et al, 2012).…”

“…Among them, BPA has been shown to bind the estrogen receptors (ERα and ERβ) (Delfosse et al, 2012), GPR30 (or GPER) (Pupo et al, 2012) and ERRγ with a high affinity (Liu et al, 2012). It also directly or indirectly interferes with the activity of the androgen receptor (AR), the progesterone receptor (PGR), the glucocorticoid receptor (GR), and the PPARγ (Acconcia et al, 2015; Rehan et al, 2015). The mechanism of action of BPA in dental cells is even less evident as its putative receptors are poorly defined in dental tissues, except for ERα (Jedeon et al, 2014a).…”