Resveratrol Acts as a Thyroid Disrupter in Normal Thyroid Cell Lines

Written by Angeline A. De Leon, Staff Writer. This in vitro and in vivo rat study suggests that resveratrol acts as a thyroid disruptor and a goitrogen and thus recommends caution when using it as a supplement or therapeutic.

Resveratrol, a natural polyphenol typically found in grapes, berries, and peanuts, possesses potent antioxidant and anti-inflammatory characteristics ^1,2. This plant compound, in the form of a dietary supplement, has demonstrated significant therapeutic efficacy against a range of chronic conditions, including diabetes, neurodegenerative disease, and cardiovascular disorders ^3,4. The anti-proliferative effects of resveratrol are also highly relevant in the context of cancer, though, in regards to thyroid cancer specifically, the effects of resveratrol treatment are still being determined ⁵. Available data thus far seems promising, suggesting that resveratrol can effectively up-regulate the expression of certain thyroid-specific genes ⁶ and increase the apoptosis of thyroid cancer cells while decreasing their proliferation ⁷. Several potential mechanisms of action have been proposed for resveratrol, including its modulation of aryl hydrocarbon receptors (AhR, involved in the regulation of thyroid function) ⁸ and its activation of sirtuins (involved in metabolic regulation) ⁹. In order to shed light on the role of resveratrol treatment in normal thyroid function, a 2017 study ¹⁰ in Food and Chemical Toxicology conducted an in vitro and in vivo investigation into the effects of resveratrol treatment on the expression of thyroid-specific genes in Sprague-Dawley rats.

In vitro experiments were conducted using samples from a rat thyroid cell line which were treated with either 10 µM resveratrol or a vehicle solution of the same amount for 6 days. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis and Western blotting were used to determine the relative mRNA expressions of thyroid-specific genes (thyrotropin receptor, TSHR; thyroid peroxidase, TPO; thyroglobulin, TG) and their relative protein expressions. In vivo experiments were carried out in a group of 12 adult male Sprague-Dawley rats, half of whom were injected with resveratrol (25 mg/kg body weight) once a day for 60 days, while the other half received a control vehicle solution. After treatment, rats were sacrificed and thyroid glands removed and analyzed for concentrations of serum thyroid stimulating hormone (TSH). Immunohistochemical analyses were also performed to evaluate cell proliferation activity in the thyroid tissue of resveratrol-treated rats.

Compared to vehicle solution, treatment with 10 µM resveratrol was found to significantly down-regulate the relative mRNA expressions of TSHR, TPO, and TG after 48 hours (p < 0.05 for all), as well as those of thyroid-specific transcription factors, Nkx2-1, Foxe1, and Pax8 after 24 hours (p < 0.05 for all). Western blot analysis also revealed a significant decrease in the expression of TSHR, TPO, and TG proteins in resveratrol-treated vs. vehicle-treated cells at the 72-hour mark (p < 0.05 for all). In vivo findings showed that relative to controls, rats receiving resveratrol treatment experienced a significant elevation in serum TSH levels (1.00 +/- 0.90 vs. 2.30 +/- 0.52 ng/mL, p < 0.05), as well as a marked increase in thyroid size (24.10 +/- 0.63 vs. 44.43 +/- 1.43 mg, p < 0.05). Finally, immunohistochemical analyses indicated an increase in the protein expression of proliferating follicular cells in the thyroids of resveratrol-treated rats vs. controls (p < 0.05).

Collectively, experimental findings suggest an opposite effect than that expected of resveratrol based on its documented anti-inflammatory and anti-proliferative effects in various diseases. In the present study, resveratrol was associated with an anti-thyroid effect, appearing to inhibit the expression of thyroid-specific genes and even inducing in vivo goitrogenic effects (relating to enlargement of thyroid) by increasing thyroid size and promoting proliferative activity of thyroid glands. Researchers hypothesize that a different mechanism may be involved in resveratrol’s action in normal vs. cancer thyroid cells. Thus, additional studies are necessary to understand this dual effect and its implications for human subjects. Based on current findings, however, supplementation with resveratrol for therapeutic purposes should be reconsidered in thyroid patients with goiter.

Source: Giuliani C, Iezzi M, Ciolli L, et al. Resveratrol has anti-thyroid effects both in vitro and in vivo. Food and Chemical Toxicology. 2017; 107: 237-247. DOI: 10.1016/j.fct.2017.06.044.

© 2017 Elsevier Ltd. All rights reserved.

Posted February 1, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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