p,p′-DDE Disturbs the Homeostasis of Thyroid Hormones via Thyroid Hormone Receptors, Transthyretin, and Hepatic Enzymes

Abstract

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-dichlorodiphenyldichloroethylene, p,p′-DDE), the major metabolite of 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and endocrine disrupting toxicant. In recent years, it has attracted many attentions on account of its disturbing effects on thyroid and thyroid hormones (THs). However, the mechanisms by which the p,p′-DDE exposure influences THs still remain uncertain. To elucidate the possible mechanisms, 20 male rats are administered with different doses of p,p′-DDE (0, 20, 60, 100 mg/kg body wt) every other day by intraperitoneal injection for 10 days. The results indicate that after the p,p′-DDE exposure, serum total thyroxine (TT4) and free thyroxine (FT4) are significantly reduced and other THs changed only little. Transthyretin (TTR) declines in serum and thyroid hormone receptors (TRα1 and TRβ1) mRNA expressions elevate in hypothalamus. The hepatic enzymes CYP1A1 (EROD), CYP2B1 (PROD), and UDPGTs are significantly upregulated, but CYP1A2 (MROD) does not show significant change. Taken together, the observed effects in the present study show that p,p′-DDE could disturb the homeostasis of THs via TRs increase, TTR decrease, and hepatic enzymes induction.

Key words

thyroid hormone - thyroid hormone receptor - enzyme

References

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