Synergistic effects of octylphenol and isobutyl paraben on the expression of calbindin-D9k in GH3 rat pituitary cells

Abstract

Abstract. Endocrine disruptors (EDs) have estrogenic activity and can cause physiological estrogenic responses. Octylphenol (OP) is one of the alkylphenolic compounds known as environmental xenoestrogens because they strongly compete with endogenous estrogens to bind to estrogen receptors (ERs). Isobutyl paraben (IBP), a widely used preservative, also exhibits estrogenic activity. Calbindin-D 9k (CaBP-9k) is a novel biomarker for the detection of EDs used in our previous studies. In this study, the CaBP-9k gene was utilized as a marker for the estrogenic activity of combined OP and IBP to investigate possible additive, synergistic or antagonistic effects of these compounds in GH3 rat pituitary cells. GH3 cells were treated with different individual or combined doses of OP and IBP. In addition, the antiestrogen ICI 182,780 was used to examine the potential involvement of ERs in the induction of CaBP-9k expression by EDs. It was found that CaBP-9k expression was significantly increased at a high-dose of OP (1 µM) combined with each dose of IBP (0.1, 1 or 10 µM) compared to all single doses of IBP and OP. A synergistic increase in luciferase activity and CaBP-9k expression was observed following combination treatment with OP and IBP. Expression of the progesterone receptor (PR) gene was similarly induced by combined treatment with OP and IBP. In addition, pre-treatment with ICI 182,780, an estrogen antagonist, significantly blunted ED-induced CaBP-9k and PR expression. In summary, the expression of CaBP-9k and PR was induced more potently by combined OP and IBP than by treatment with either ED alone. ICI 182,780 treatment reversed ED-induced CaBP-9k and PR expression in these cells. Taken together, these results indicate that combined exposure to OP and IBP has a synergistic effect on the induction of CaBP-9k and PR gene expression via an ER-dependent pathway in GH3 cells.

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

“…Thus, some significant associations reported in our exploratory work here may be due to chance. Mixtures of the exposures were also not considered for these preliminary analyses, even though some phenol and paraben mixtures have been associated with adverse reproductive outcomes (Isling et al, 2014; Kim et al, 2012; Popa et al, 2014). We will consider this possibility in our future work with larger sample sizes, as well as explore potential differences by infant sex.…”

Advanced Oxidation Kinetics and Mechanism of Preservative Propylparaben Degradation in Aqueous Suspension of TiO2 and Risk Assessment of Its Degradation Products

“…Thus the presence of trace amounts of parabens also may be a risk because of their combined effects with other toxic pollutants. 10 It is therefore essential to investigate the transfer and transformation characteristics, fate, and potential risk of PPB in water. The degradation kinetics, mechanism, and risk assessment of PPB by advanced oxidation processes (AOPs) to eliminate PPB from water should also be considered.…”

Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane

“…In this study, expression of CaBP-9K was highly induced by E2 and slightly increased by D4 in GH3 cells. Many previous studies have demonstrated that CaBP-9K expression is induced by various EDs both in vitro and in vivo [ 31 , 32 , 33 ], including in GH3 cells [ 34 , 35 ]. ICI, an ER α inhibitor, decreased CaBP-9K expression elevated by E2 and D4.…”