Thyroid hormone disrupting potentials of bisphenol A and its analogues - in vitro comparison study employing rat pituitary (GH3) and thyroid follicular (FRTL-5) cells.
As adverse health effects of bisphenol A (BPA) become a growing public health concern, the chemicals substituting BPA have been increasingly used in everyday lives. BPA substitutes have been frequently detected in both environment and biota in increasing levels. However, very limited toxicological information is available for these chemicals. In the present study, thyroid disrupting effects of nine structural analogues of BPA were evaluated along with BPA, using rat pituitary (GH3) and thyroid follicular (FRTL-5) cells. Similar to BPA, its analogues caused significant down-regulation of tshβ, trα, trβ, dio1 or dio2 genes in GH3 cells, and some analogues, such as BPF, BPM or BPZ, showed even greater potency compared to BPA. In FRTL-5 cells, the genes responsible for hormone synthesis, e.g., pax8, nis, tg or tpo genes, exhibited over 1.5-fold up-regulation following exposure to BPA analogues, such as BPS. The effects on gene regulation was different by the cell line. Our results clearly show that the BPA substituting chemicals may influence thyroid hormone homeostasis by affecting thyroid regulation and hormone synthesis, often at lower doses compared to BPA. Thyroid effects of the BPA analogues deserve further investigations in experimental organisms and in human populations.
School of Public Health, Seoul National University, Seoul 08826, Republic of Korea; System Toxicology Research Center, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
Sangwoo
S
Lee
School of Public Health, Seoul National University, Seoul 08826, Republic of Korea; CRI Global Institute of Toxicology, Croen Research Inc., Suwon 16614, Republic of Korea.
Cheolmin
C
Kim
Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, 03080, Republic of Korea; Tumor Microenvironment Global Care Research Center, Cancer Research Institute, College of Medicine, Seoul National University, 03087, Republic of Korea.
Hyewon
H
Youn
School of Public Health, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: kyungho@snu.ac.kr.
Kyungho
K
Choi
D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D010911:Pituitary Neoplasms / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology; D013963:Thyroid Hormones / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D013963:Thyroid Hormones; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Alternative chemical; Cell line; Endocrine disruption; Substitute; Thyroid hormone