Thyroid hormone is synthesized in the colloid of follicles in the thyroid gland. The colloid contains substances secreted from follicular cells, including thyroglobulin, iodide, and enzymes necessary for the synthesis of thyroid hormone. Thyroglobulin is the precursor for the thyroid hormones.
Thyroglobulin is a protein with
tyrosine residues, which become iodinated. The tyrosine can have one iodide attached to it to form monoiodotyrosine (MIT) or two iodides to form diiodotyrosine (DIT). Within a single thyroglobulin molecule, coupling takes place between either an MIT and DIT, or two DIT, in which a covalent bond is formed resulting in the produced of T3 and T4, the two thyroid hormones.
T3 and T4 remain attached to the thyroglobulin in the colloid for up to three months. Release of the thyroid hormones is under control of the anterior pituitary tropic hormone TSH (which is under control of the hypothalamic tropic hormone TRH). TSH binds to receptors on the plasma membrane of follicular cells, activating the enzyme adenylate cyclase, which then converts ATP to cAMP. cAMP produces a variety of responses that lead to the release of thyroid hormones. First, thyroglobins with attached thyroid hormones are brought into the follicular cell by
phagocytosis. The resulting phagosome fuses with a lysosome. Enzymes in the lysosome catalyze the release of T3 and T4 from thyroglobulin, and these two thyroid hormones diffuse out of the follicular cell and into the bloodstream.
Ten times more T4 is released than T3, but T3 is four times more active at target cells than T4. After its release, T4 is converted into T3 by the liver, kidneys, and target cells. T4 also provides long-loop negative feedback to the release of TRH and TSH.
Thyroid hormone receptors are located in the nucleus of target cells, where thyroid hormones alter the transcription of mRNA.
The primary action of
thyroid hormone is to increase metabolic rate (increase oxygen consumption). Thyroid hormone increases metabolic rate by increasing Na+/K+ pump activity, increasing the number of mitochondria, and increasing the concentration of oxidative phosphorylation enzymes. In addition to increased energy use, high concentrations of thyroid hormone increases energy mobilization by promoting glycogenolysis, degradation of protein to amino acids, lipolysis, gluconeogenesis, and ketone synthesis. Lower concentrations of thyroid hormone promote glycogenesis and protein synthesis. Many of the effects of thyroid hormone are permissive.
Thyroid hormone promotes synthesis of beta adrenergic receptors, which enhance a cell's responses to sympathetic nervous activity. Also, thyroid hormone is necessary for normal growth and development of nerves. Thyroid hormone stimulates growth hormone release and is permissive to the action of growth hormone.