Thyroid Hormone Synthesis and Functions

Anatomy of Thyroid Gland

• The thyroid gland is one of the largest endocrine glands in the body, with a butterfly-shaped structure consisting of two lobes connected by an isthmus.
• It is situated on the front sides of the trachea and located below the larynx.

Thyroid Follicle

• The thyroid follicle is the functional unit of the thyroid gland, with a spherical structure lined with follicular cells.
• The follicular cavity is filled with a gel-like viscous iodine-rich material called thyroid colloid, which contains a protein called thyroglobulin.

Parafollicular Cells (C Cells)

• Parafollicular cells are located between the follicles and secrete calcitonin, which decreases blood calcium levels.

Functions of Thyroid Gland

• The thyroid gland secretes two main hormones: thyroxine (T4) and triiodothyronine (T3), which regulate the body's metabolic rate and are necessary for normal growth and development.
• The gland also secretes calcitonin, which decreases blood calcium levels.

Synthesis of Thyroid Hormone

• Thyroglobulin is synthesized in follicular cells and discharged into the lumen of the follicle.
• Iodide is actively taken up from the blood by follicular cells through a sodium-iodide symporter.
• Iodide is then oxidized to active iodine (I2) by thyroperoxidase (TPO) and transported into the lumen of the follicle.
• Iodine is attached to tyrosine, forming mono-iodotyrosine (MIT) and di-iodotyrosine (DIT), which then link together to form T3 and T4.
• T4 is formed from 2 molecules of DIT, while T3 is formed from 1 molecule of DIT and MIT.

Control of Thyroid Hormone Synthesis and Secretion

• The thyroid gland is controlled by hormone secretions from the hypothalamic-pituitary-thyroid axis.
• The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary.
• TSH stimulates the production of T3 and T4 from the thyroid gland, which in turn exerts negative feedback on the pituitary and hypothalamus.

Transport of Thyroid Hormone

• Thyroid hormones are hydrophobic and are found in the circulation associated with plasma-binding proteins, including thyroxine-binding globulin (TBG), pre-albumin, and albumin.
• Less than 1% of thyroid hormone is found free in the circulation.

Metabolism of Thyroid Hormone

• Approximately 100 μg of thyroid hormones are secreted from the gland each day, mostly in the form of T4 with about 10% as T3.
• About 80% of T4 undergoes peripheral conversion to T3 in the liver and kidney, or to reverse T3 (rT3).

Mechanism of Action

• T3 enters the nucleus and binds to a specific nuclear thyroid hormone receptor (TR), which binds to DNA at specific sequences called thyroid hormone response elements (TRE).
• This increases the expression of various genes that code for proteins that regulate cell functions.

Functions of Thyroid Hormone

• Thyroid hormone plays a crucial role in regulating the body's metabolic rate and is necessary for normal growth and development.