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Thyroid Hormone Action

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p739-740

2026-07-02

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 Circulating thyroid hormone levels are maintained in the euthyroid range by a classical negative feedback loop. Thyrotropin releasing hormone (TRH) is synthesized in the paraventricular nucleus of the hypothalamus and stimulates synthesis and secretion of TSH by the anterior pituitary gland. TSH, acting via the G- protein coupled TSH receptor, stimulates growth of thyroid follicular cells and the synthesis and release of thyroid hormones. Thyroid hormones act via thyroid hormone receptors in the hypothalamus and pituitary to inhibit TRH and TSH synthesis and secretion. This feedback loop maintains circulating thyroid hormones and TSH in a physiological inverse relationship that defines the hypothalamic- pituitary- thyroid (HPT) axis set point.

The thyroid gland secretes the pro- hormone T4 and a small amount of the active hormone 3,5,3′- L- triiodothyronine (T3). Circulating T4 levels are maintained at approximately 3– 4- fold higher concentrations than T3. Intracellular availability of T3 is determined by active uptake by specific cell membrane transporters including monocarboxylate transporter- 8 (MCT8), MCT10 and organic acid transporter protein- 1c1 (OATP1c1), and by the activities of the type 2 and 3 deiodinase enzymes (D2 and D3). D2 con verts T4 to T3 by catalysing removal of a 5′- iodine atom. By contrast, D3 prevents activation of T4 and inactivates T3 by removal of a 5- iodine atom to generate the metabolites 3,3′,5′- L- triiodothyronine (reverse T3) and 3,3′- diiodothyronine (T2), respectively. Thus, the relative levels of D2 and D3 determine the concentration of intra cellular T3 available to the nuclear receptors (TRs).

TRs act as hormone inducible transcription factors that regulate expression of T3- responsive target genes. The THRA and THRB genes encode three functional TRs, TRα1, TRβ1, and TRβ2. TRα1 and TRβ1 are widely expressed but with developmental and tissue specific regulation of their relative levels. Expression of TRβ2 is mainly restricted to the hypothalamus and pituitary where it mediates inhibition of TRH and TSH expression.