Role of estrogen receptors in thyroid toxicity induced by mono (2-ethylhexyl) phthalate via endoplasmic reticulum stress: An in vitro mechanistic investigation.

Mono(2-ethylhexyl) phthalate (MEHP) can influence the expression of estrogen receptors (ERs) and induce thyroid injury. The expression of ERs can be related to thyroid disease and abnormal expression of ERs has been associated with activation of endoplasmic reticulum stress. This study aimed to clarify the role of ERs in MEHP-induced thyroid damage via endoplasmic reticulum stress. We exposed Nthy-ori 3-1 cells to different doses of MEHP. We found that after the exposure, the cell viability and the expression levels of thyroid hormone metabolism-related proteins decreased, while the apoptosis level and the expression levels of ERs (ERα and GPR30) increased. Three endoplasmic reticulum stress-related signaling pathways were activated by MEHP. After ERα and GPR30 were knocked down, these three pathways were inhibited and the thyroid toxicity was alleviated. Taken together, our results indicate that MEHP can induce thyroid toxicity by upregulating the expression of ERs, further activating endoplasmic reticulum stress.