Thyroid Hormone Transport
- Thyroid hormones are present in the blood either bound or unbound to plasma proteins. Importantly, free, unbound thyroid hormones are the only form that has endocrine activity as it can freely diffuse through cellular plasma membranes and thus bind the cytosolic thyroid hormone nuclear receptor. However, the majority of thyroid hormones in the blood are non-covalently bound by the plasma protein Thyroxine-binding Globulin (TBG) produced by the liver. The TBG-bound thyroid hormones do not possess any endocrine activity because they cannot cross plasma membranes of cells, however, TBG-bound thyroid hormone does act as a reservoir of the hormone in the body.
- Importantly, free, unbound and TBG-bound thyroid hormones are in dynamic equilibrium with one another. Consequently, increases or decreases of TBG concentration in the body will affect free, unbound thyroid hormone levels and thus can modulate the endocrine activity of the hormones. However, this is not a physiological regulatory mechanism and only occurs in some pathological scenarios. For example, decreased hepatic synthesis of TBG during hepatic failure can cause a transient increase in free, unbound thyroid hormone levels and thus transiently increased thyroid hormone endocrine activity.