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The Flavonoid Quercetin Regulates Growth and Gene Expression in Rat FRTL-5 Thyroid Cells

Department of Medicine and Sciences of Aging (C.G., G.N., I.B., F.M.), Unit of Endocrinology, and Department of Oncology and Neurosciences (D.T., M.P.), University "G. D’Annunzio" and Aging Research Center, Centro Scienze dell’Invecchiamento, "Gabriele D’Annunzio" University Foundation, 66013 Chieti, Italy; and Edison Biotechnology Institute and Department of Biomedical Sciences (Y.N., N.H., L.D.K.), College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701

Address all correspondence and requests for reprints to: Dr. Cesidio Giuliani, Unit of Endocrinology, Centro Scienze dell’Invecchiamento, Fondazione Universita’ "Gabriele D’Annunzio" Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy. E-mail: cgiulian{at}unich.it.

Quercetin is the most consumed flavonoid present in fruits and vegetables. There has been increased interest in the possible health benefits of quercetin and other flavonoids. Because it is reported that these compounds have some antithyroid properties, we were interested whether, and by what mechanism, quercetin might regulate thyroid cell growth and function. In this report we show that quercetin inhibits thyroid cell growth in association with inhibition of insulin-modulated phosphatidylinositol 3-kinase-Akt kinase activity. Furthermore, quercetin decreases TSH-modulated RNA levels of the thyroid-restricted gene sodium/iodide symporter (NIS). We associated down-regulation of NIS RNA levels with inhibition of iodide uptake at comparable quercetin concentrations and could show that the inhibitory effect of quercetin on NIS RNA levels and iodide uptake is reproduced by inhibitors of the phospholipase-A₂/lipoxygenase pathway. The specific inhibitor of protein kinase A, H89, only partially inhibited TSH-increased NIS expression and did not reproduce the quercetin effect. The quercetin studies thus reveal that the phospholipase-A₂/lipoxygenase pathway appears to play an important role in TSH regulation of NIS gene expression, whereas quercetin inhibition of growth appears to involve an effect on insulin/IGF-I-Akt signaling. The data raise the possibility that quercetin may be a novel disruptor of thyroid function, which has potential effects on, or use in, the therapy of thyroid diseases.