Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

Abstract

Plastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

Bisphenols as Environmental Triggers of Thyroid Dysfunction: Clues and Evidence

“…Transcriptional levels of deiodinases were more elevated in exposed zebrafish, in accordance with a study reporting that hypothyroidism caused by EDCs is associated with higher activity and expression of Dio2 [164]. On the other hand, a recent study reported a reduction of liver DIO1 activity in BPA-treated adult rats [102], which is a finding worth of note as decreased expression of DIO1 was observed in nearly all PTCs and is likely an early event in malignant TC [165].…”

“…Adult males treated with BPA showed a decrease activity of hepatic DIO1, coherently with what has been reported in vitro [102]. Moreover, in female adult rats BPA lowered thyroid iodide uptake and thyroid peroxidase (TPO) activity, which are two essential steps in TH biosynthesis, probably due to an elevation of reactive oxygen species (ROS) production.…”

“…BPA inhibited the activities of DIO1 and DIO2 [102], and both BPA and TBBPA markedly dysregulated transcription of Dio3, which is responsible for protection of tissues from TH excess and is the predominant deiodinase expressed in human placenta [103], and hepatic phase II metabolizing genes (Sulfotransferases (Sult1) and UDP-glucuronosyltransferases (Ugt)) [75]. TBBPA, but not BPA, increased expression of the Ttr gene [75], an action at mRNA level that corroborates the competing binding capabilities of TBBPA with TTR [70,84].…”

“…Indeed, Zoeller et al [104] and Zhang et al [105] observed a significant increase of serum T4 levels in pups of both sexes and in female adults, respectively, without any apparent interference on TSH release. In male adult rats, treatment with BPA led to an increase of T4 levels and a reduction of the T3/T4 ratio, suggesting that in exposed animals BPA may impair the peripheral conversion of T4 to T3 [102].…”

Bisphenols as a Legacy Pollutant, and Their Effects on Organ Vulnerability

“…Bisphenols are also reported to bind to the α and β receptors of fatty tissues and modulate their functions. BPA exposure also disrupts thyroid signaling by affecting the metabolism of the thyroid hormone [101].…”