Endocrine Abstracts

Bisphenol A (BPA) is a widely used chemical and belongs to the list of metabolism-disrupting chemicals. BPA is banned in several countries and replaced by others BPA-analogs. We investigate the effects of BPA and 6 BPA-analogs (BPS, BPAF, BPF, BPB and BADGE) on the response of the human melanocortin 4 receptor (MC4R), a receptor involved in food intake and weight control, to its natural ligands. We used HEK293 cells line transiently transfected with human MC4R to determine the impact of bisphenols on MC4R-dependent cAMP production. BPAF (10⁻¹¹M) and BPF (10⁻¹¹M) were the most potent positive modulators of α Melanocortin-Stimulating Hormone (MSH) response, followed by BPB (10⁻⁹M) = BADGE (10⁻⁹M) > BPS (10⁻⁸M) = BPA (10⁻⁸M). Moreover, BPA (10⁻⁸M) impaired the response of MC4R to the Agouti-related Peptide (AgRP), a natural inverse agonist of the receptor. In HEK293 mock-transfected cells, bisphenols had no effect on basal or adenosine induced cAMP response. Thus, the potentiating effect of bisphenols was dependent on and specific of the MC4R. In opposite, we showed that BPA and BPA-analogs reduced by half the response of melanocortin 3 receptor to α MSH. In conclusion, our in vitro findings suggest that human MC4R is a target for both BPA and BPA-analogs. These findings highlight that BPA analogs retain an activity similar to that of BPA and thus they may still remain potential metabolism-disrupting chemicals.