Novel insights into di‑(2‑ethylhexyl)phthalate activation: Implications for the hypothalamus‑pituitary‑thyroid axis

Abstract

Di (2‑ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamic‑pituitary‑thyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHP‑stimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, bio‑transportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroid‑stimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrine‑disrupting activities of phthalates and the molecular mechanisms of DEHP‑induced thyrotoxicity.

Keywords: hormone homeostasis; di‑(2‑ethylhexyl)phthalate, thyroid; hypothalamus‑pituitary‑thyroid axis; thyroid‑stimulating hormone/thyroid‑stimulating hormone receptor signaling.