16.7-16.10

The Thyroid Gland Controls Metabolism

Anatomy and Structure

The thyroid gland is the largest pure endocrine gland in the human body and plays a crucial role in regulating metabolism. It is located on the anterior aspect of the trachea, just inferior to the larynx.

• Shape and Location: Butterfly-shaped, consisting of two lateral lobes connected by a median tissue mass called the isthmus.

• Follicles: The gland contains spherical follicles filled with colloid, surrounded by epithelial follicular cells that produce the glycoprotein thyroglobulin.

• Colloid: A thick fluid containing thyroglobulin proteins with attached iodine, serving as the precursor for thyroid hormone synthesis.

• Parafollicular cells: Located around the follicles, these cells produce the hormone calcitonin.

Example: Figure 16.8 illustrates the gross anatomy and histology of the thyroid gland, showing the location of follicles, follicular cells, and parafollicular cells.

Thyroid Hormone: Synthesis and Function

Thyroid Hormone Forms and Properties

The thyroid hormone (TH) is the body's major metabolic hormone, affecting nearly all cells. It is produced in two forms:

• Tetraiodothyronine (T4) or Thyroxine: Consists of two tyrosine molecules with four bound iodine atoms.

• Triiodothyronine (T3): Consists of two tyrosine molecules with three bound iodine atoms.

• Unlike other amines, TH is lipid-soluble (similar to steroids), must travel in the bloodstream bound to carrier proteins, and can enter target cells to bind to intracellular receptors within the nucleus, triggering transcription of various genes for protein synthesis.

Additional info: T3 is the more active form at target tissues.

Physiological Effects of Thyroid Hormone

Thyroid hormone exerts multiple effects on the body:

• Increases basal metabolic rate and heat production (calorigenic effect).

• Regulates tissue growth and development: Essential for normal skeletal and nervous system development and reproductive capabilities.

• Permissive for epinephrine and norepinephrine: Maintains normal numbers of adrenergic receptors in blood vessels, which is necessary for proper blood pressure regulation.

Synthesis of Thyroid Hormone

Thyroid hormone is synthesized in seven steps and stored extracellularly in the colloid of follicles:

1. Thyroglobulin synthesis: Produced by follicular cells and transported into the follicle lumen.

2. Iodide uptake: Iodide ions are actively taken into the cell and transported into the follicle lumen.

3. Iodide oxidation: Iodide is oxidized (electrons removed) into iodine.

4. Iodine attachment to tyrosine: Via peroxidase enzymes:

   • One iodine + tyrosine = Monoiodotyrosine (MIT)

   • Two iodines + tyrosine = Diiodotyrosine (DIT)

5. Coupling of iodinated tyrosines: MIT and DIT link to form T3 and T4.

6. Endocytosis: Colloid with thyroglobulin is brought into follicular cells via endocytosis.

7. Release: Lysosomal enzymes release T3 and T4 from thyroglobulin, which are then secreted (via simple diffusion) from the follicular cells.

Example: The process of MIT and DIT coupling is essential for the formation of active thyroid hormones.

Transport and Regulation of Thyroid Hormone

Thyroid hormones are transported in the blood by thyroxine-binding globulins (TBG). Both T3 and T4 bind to target receptors, but T3 is about ten times more active. Target tissues have enzymes that convert T4 to T3 by removing an iodine atom.

• Regulation: Release of thyroid hormone is regulated by negative feedback:

  • Falling TH levels stimulate release of thyroid-stimulating hormone (TSH).

  • Rising TH levels (as well as GHIH, dopamine, and cortisol) inhibit TSH release.

  • Thyrotropin-releasing hormone (TRH) from the hypothalamus can override negative feedback during pregnancy or cold exposure, especially in infants.

Additional info: This regulatory mechanism ensures stable metabolic activity and adaptation to physiological demands.