The Flavonoid Xanthohumol affects Thyroid Hormone Binding in Human and Rat Serum

The most potent natural and synthetic plant derivatives affecting thyroid function and secretion are flavonoids. In the normal adult rat, thyroid hormones are transported to target tissues primarily bound to transthyretin (TTR). This is in contrast to human serum, where thyroxine-binding globulin (TBG) binds T4 with highest affinity. Flavonoids are strongly and preferentially bound to TTR in most species including man but show no or only minor competition for thyroid hormone bound to TBG, or to serum albumin. Xanthohumol is the major prenylated flavonoid of the female inflorescences (cones) of the hop plant (Humulus lupulus). It is also a constituent of beer, our major dietary source of prenylated flavonoids. In the present study, we analysed the effects of Xanthohumol on the thyroid hormone axis, in particular the binding of T4 to its transport and distributor proteins in human as well as in rat serum.

Serum binding of 125I-labeled L-T4 was analyzed in the absence or presence of increasing concentrations of Xanthohumol using nondenaturing PAGE gels. A phosphoimager-based analysis quantified the binding and distribution of T4 among the individual binding proteins. Our results confirmed the highest affinity of rat TTR and human TBG to bind [125I] T4. Marked displacement of [125I] T4 binding to TTR was observed in human as well as rat sera incubated with Xanthohumol at concentrations >100µM. The labelled hormone was displaced to albumin in rat and to TBG in human serum. The inhibitory effect of Xanthohumol was confirmed in direct binding assays using purified TTR and dextran coated charcoal for separation of free from bound T4. 50% displacement of 125I-labeled L-T4 from human TTR was observed at a concentration of 100nM-1µM.

This study revealed a potent and selective competition of the flavonoid Xanthohumol for T4 binding to TTR similar to other flavonoids and emphasizes its potential disruption effect on the thyroid hormone axis beyond previous reports on its interference in the steroid hormone system.

Supported by DFG.