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Identifying the Underlying Mechanism of BPA down regulation of Pomc gene expression in mice

BPA is an industrial chemical used to make flame-retardant materials, plastics, receipts and the coating to food containers. More importantly, BPA has been shown to act as a weak xenoestrogen when ingested, dermally absorbed or inhaled. Studies have shown that low dose BPA exposure during perinatal periods can have a significant impact on the Hypothalamic Pituitary Adrenal (HPA) axis. This influence on the HPA axis can lead to various mental disorders such as depression, bipolar disorder and anxiety. However, little is known about BPA’s influence at the level of the pituitary, specifically in corticotrophs. The postnatal time period is a crucial window of development for the pituitary and disruption in its growth can result in adverse effects. In our lab, we focus on the effects of BPA on the developing pituitary of postnatal mice. Our current studies involved an in vivo mouse model in which mice were dosed with various amounts of BPA. To determine the effects of BPA exposure on the pituitary, mice were orally dosed 0.05 μg/kg/day, 0.5μg/kg/day, human relevant doses of BPA, 50μg/kg/day, the oral reference dose, and 50μg/kg/day estradiol (E2), to induce expression of E2 regulated genes. Results also showed a significant decrease in Pomc mRNA levels in females at 0.5μg/kg/day and 50μg/kg/day BPA. Whereas males experienced a significant decrease in Pomc mRNA levels at 0.5μg/kg/day. Estradiol exposure decreased Pomc gene expression in both males and females. The effects of BPA on Pomc expression appeared to be sex dependent, so our lab decided to run experiments to further investigate. Specifically, identifying the mechanism in which BPA down regulates Pomc mRNA levels. In our studies, pituitary explants were treated in culture with the estrogen receptor agonists of Esr1, Esr2 and Gpr30. Our results revealed activation of Gpr30 in males led to a significant decrease in Pomc mRNA levels, whereas activation of both Esr1 and Esr2 led to a significant decrease of Pomc mRNA levels in females. This data indicates that BPA repression of Pomc mRNA levels may regulate differently in males and females. Overall, our studies suggest that BPA downregulates Pomc expression using a sex dependent mechanism.

John de Graft-Johnson
University of Maryland Baltimore County
Chemical Engineering
Research Advisor: 
Dr. Lori Raetzman
Department of Research Advisor: 
Molecular & Integrative Physiology
Year of Publication: