Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity

Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent co ntaminants giving rise to potential health hazard. Some PCBs exert dioxin-l ike activities mediated through the aryl hydrocarbon receptor. Although rep orts on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we presen t evidence that the three PCBs most abundant in biological extracts, 2,2',3 '4,4',5-hexachlorobiphenyl (PCB # 138), 2,2',4,4',5,5'-hexachlorobiphenyl ( PCB # 153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB # 180) have pleio tropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a sli ghtly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17 beta -Estradiol. whereas the compo unds inhibited cell growth significantly at 1 and 10 muM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estroge n receptor-ligand mediated decrease of the chloramphenicol transferase acti vity in both control and 10 nM 17 beta -estradiol induced MCF-7 cells. In a ddition, PCB # 138 elicited a dose-dependent antagonistic effect on androge n receptor activity in transiently co-transfected Chinese Hamster Ovary cel ls with an IC50, of 6.2 muM. In summary, this study indicate that the di-or tho, multiple-chloro substituted biphenyls, PCB # 138, PCB # 153 and PCB # 180, can compete with the binding of the natural ligand to two nuclear rece ptors and thus possess the ability to interfere with sexual hormone regulat ed processes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.