Thyroid Hormone Production and Biosynthesis

Thyroid Hormone Production

• Calorigenesis: Thyroid hormones increase heat production in the body.
• Cholesterol Reduction: Thyroid hormones decrease hepatic LDL receptors, leading to lower total cholesterol.
• Cardiovascular Effects: Thyroid hormones have an inotropic effect, increasing beta receptor activity. This leads to increased heart rate, cardiac output, and blood pressure.
• Fluid Retention: Thyroid hormones promote fluid retention.

Thyroid Hormone Biosynthesis

• Location: Biosynthesis of T3 and T4 occurs in follicular cells of the thyroid gland. Calcitonin is produced in parafollicular (C) cells.
• Iodide Uptake: Iodide enters follicular cells via the sodium/iodide symporter (NIS). High levels of iodide inhibit this process and overall thyroid hormone synthesis. Other anions, like thiocyanate (SCN-), pertechnetate (TcO4-), and perchlorate (ClO4-) can also inhibit iodide uptake.

Peroxidase-Mediated Steps

• Enzyme: Thyroid peroxidase (TPO) is the key enzyme. TSH from the anterior pituitary increases TPO production, stimulating thyroid hormone release.
• Peroxidation: Iodide is oxidized to iodine by thyroid peroxidase, a critical step in thyroid hormone synthesis. High iodide levels and thioamide drugs can block this peroxidation (and other steps that depend on TPO).
• Organification: Iodine is incorporated into tyrosine residues within the thyroglobulin protein molecule. This results in monoiodotyrosine (MIT) and diiodotyrosine (DIT).
• Coupling: MIT and DIT combine, forming T3 (triiodothyronine). Two DITs combine to form T4 (thyroxine). T3 and T4 are still bound to thyroglobulin at this point.