Dong, X; Dong, J; Zhao, Y; Guo, J; Wang, Z; Liu, M; Zhang, Y; Na, X
Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats' thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.
Animals; Autoantigens/drug effects; Diethylhexyl Phthalate/pharmacology; Dose-Response Relationship, Drug; Hypothalamus/drug effects; Iodide Peroxidase/drug effects; Iron-Binding Proteins/drug effects; Nuclear Proteins/drug effects; Pituitary Gland/drug effects; Pituitary Hormones/metabolism; Rats, Wistar; Thyroid Gland/drug effects; Thyroid Hormones/metabolism; Thyroid Nuclear Factor 1; Thyrotropin/metabolism; Transcription Factors/drug effects; TSH/TSHR; hypothalamus-pituitary-thyroid axis; molecular mechanisms; signaling pathways; thyroid function; 9002-71-5; C42K0PH13C