Biosynthesis, transport, metabolism, and actions of thyroid hormones

Abstract

In healthy humans with a normal iodine intake, the thyroid follicular cells produce predominantly the prohormone thyroxine (3,3′,5,5′-tetraiodothyronine; T4), which is converted in peripheral tissues to the bioactive hormone 3,3′,5-triiodothyronine (T3) or to the inactive metabolite 3,3′,5′-triiodothyronine (reverse T3). The bioavailability of thyroid hormone in target tissues depends to a large extent on the supply of plasma T4 and T3, the activity of transporters mediating the cellular uptake and/or efflux of these hormones, as well as the activity of deiodinases and possibly other enzymes catalyzing their activation or inactivation. Thyroid function is regulated most importantly by the hypophyseal glycoprotein thyroid-stimulating hormone (TSH), also called thyrotropin. In turn, TSH secretion from the anterior pituitary is stimulated by the hypothalamic factor thyrotropin-releasing hormone (TRH). TSH secretion is down-regulated by negative feedback action of thyroid hormone on the hypothalamus and the pituitary. The contribution of locally produced T3 versus uptake of plasma T3 is much greater for some tissues such as the brain and the pituitary than for most other tissues. Plasma TSH is an important parameter for the diagnosis of thyroid dysfunction but is not representative for the thyroid state of all tissues. In this chapter various aspects will be discussed of: (a) the neuroendocrine regulation of thyroid function, (b) the biosynthesis of thyroid hormone (i.e. the prohormone T4), (c) the activation and inactivation of thyroid hormone in peripheral tissues, and (d) the mechanism by which T3 exerts it biological activity. A schematic overview of the hypothalamus– pituitary–thyroid–periphery axis is presented in Fig. 3.1.2.1.