Effects of isoflavonoids and other plant-derived compounds on the hypothalamus–pituitary–thyroid hormone axis

Abstract 

Objectives

There is increasing concern that exposure to flavonoids may lead to endocrine disruption of the hypothalamus–pituitary–thyroid hormone axis, and, additionally, there is evidence that secondary plant metabolites contained in our daily diet or used for hormone-replacement therapy act as hormones themselves, similar to known isoflavonoid effects in the steroid hormone network. These compounds of natural origin affect the thyroid hormone feedback system by interference with different components of this homeostatically regulated system: biosynthesis, secretion and metabolism, transport, distribution, and action of thyroid hormones including the feedback mechanism. Genistein and daidzein, the major components of soy, influence thyroid hormone synthesis by inhibition of the iodide oxidizing enzyme thyroperoxidase, interfere with thyroid hormone transport proteins and 5′-deiodinase type I activities in peripheral tissues, which leads to altered thyroid hormone action at the cellular level. Synthetic flavonoids, such as F21388, structurally similar to thyroxine, cross the placenta and reach the fetal brain of animal models also.

Methods

A review of effects of various isoflavonoids and plant-derived extracts on the hypothalamus–pituitary–thyroid axis is the major objective of this contribution. In addition, new experimental data obtained in ovariectomized (ovx) rats will be presented. The substances tested here were plant extracts of Agnus castus, Belamcanda chinensis, Silybum marianum, Cimicifuga racemosa, and a commercially available soy product.

Results

In ovx rats the extract at two doses showed no effects on circulating TSH and thyroid hormone serum levels after 3 months of treatment.

Conclusion

The thyroid hormone network has a considerable capacity to compensate for disturbances of this feedback system as it is necessary for various metabolic and catabolic reactions and development. With respect to still insufficient nutritive iodine-supply of almost one third of the world population, possible adverse flavonoid actions on the thyroid hormone axis have to be examined more closely.

Keywords: Isoflavonoid, Secondary plant metabolites, Soy, Genistein, Cimicifuga racemosa, Thyroid hormone, Thyroperoxidase, Transthyretin, 5′-Deiodinase