Abstract
Consumption of soya-based nutrients is increasing in modern society because of their potentially protective effects against chronic diseases. Soya products are also heavily advertised as alternative drugs for relief from symptoms of the menopause and for hormone replacement therapy. However, because of their oestrogenic activity, negative effects of isoflavones have been postulated. Therefore, we analysed influences of soya isoflavones, major soya constituents with endocrine activity, on thyroxine (T4) binding to its distribution proteins. Serum binding of (125)I-labelled L-T4 was analysed in the absence or presence of increasing concentrations of soya isoflavones using non-denaturing PAGE for analysis. Complete displacement of [(125)I]T4 binding to transthyretin (TTR) was observed in human serum incubated with genistein at concentrations >10 microM; interference started at >0.1 microM. Glycitein showed decreased and daidzein the lowest displacement potency. [(125)I]T4 was displaced to albumin in rat and to T4-binding globulin in human serum. Soya isoflavones also obstruct [(125)I]T4 binding to TTR in human cerebrospinal fluid (CSF). The inhibitory effect was confirmed in direct binding assays using purified TTR with 50% inhibitory concentration values of 0.07 microM for genistein, 0.2 microM for glycitein and 1.8 microM for daidzein. The present study underlined a potent competition of soya isoflavones for T4 binding to TTR in serum and CSF. Isoflavones might alter free thyroid hormone concentrations resulting in altered tissue availability and metabolism. As a consequence of this interference, one could expect a disturbance in the feedback regulation of hormonal networks, including the pituitary-thyroid-periphery axis during development and in adult organisms.
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