Thyroid hormone effects every cell

Thyroid hormone affects virtually every cell in the body. The thyroid system provides an example of how the endocrine system and the nervous system can functionally merge to achieve an objective. Thyroid hormone is crucial to growth, nutrient metabolism and body heat generation. Among numerous other things, it supports neuron maturation in infants and assists pituitary growth hormone in regulation of long bone growth.

Thyroid histology

The thyroid gland, a butterfly-shaped organ situated on the anterior side of the neck, lies around the larynx and trachea below the Adam’s apple. On it lays the parathyroid gland.

Histology section showing thyroid follicles, Vetpathologist/Shutterstock.com

At the microscopic level, the thyroid gland contains spherical structures called follicles where hormone is synthesized.

This photomicrograph shows a section of thyroid gland on the left and adjacent parathyroid gland on the right. Notice the structural difference in the two types of tissue. The center of each thyroid follicle is filled with a colloid material. In this section the thyroid cells are at the edges of the colloid.

Thyroid hormone synthesis

Follicle cells increase their synthesis of thyroid hormone in response to the blood presence of another hormone name Thyroid Stimulating Hormone (TSH). TSH is secreted by the pituitary gland and binds to a plasma membrane receptor on thyroid follicle cells. This sets in motion cellular pathways for the synthesis of thyroid hormone.

Steps in the synthesis of thyroid hormone and its release into blood, Public Domain/Wikimedia Commons

The initial step in thyroid hormone synthesis is production of a protein called thyroglobulin on the rough endoplasmic reticulum of the follicle cells. Thyroglobulin is transferred from the cell into the central colloid material by exocytosis. In the colloid of the follicle iodine is added to the thyroglobulin.

Iodide (I^–) is pumped into the follicle cells from the capillaries supplying the follicle cells. As the concentration of I^– increases in the cell it is passively transported into the central colloid. I^– in the colloid is oxidized by an enzyme reaction to iodine (I⁰), a highly reactive molecule.

I⁰ combines with the many tyrosine residues of thyroglobulin. Iodinated thyroglobulin then reenters the follicle cell by endocytosis. Various cell enzymes that break apart proteins named proteases excise thyroxine (T4) with four attached iodine and triiodothyronine (T3) with three attached iodine. Cell membrane transporters then move T4 and T3 into blood capillaries.

Most, 80% of thyroid hormone leaving the gland is T4. In the blood, these small molecules are bound to large globular plasma proteins. Only about 1% of it is free and available for cellular uptake.

Thyroid hormone receptor

For a target cell to respond to a hormone it must have a receptor, a cell protein that binds to the hormone. Thyroid hormone receptors reside in the cell nucleus. Because thyroid hormone is not lipid soluble, it enters the target cell with the help of membrane transporters located in the plasma membrane to reach its receptors.

There are multiple types of thyroid hormone receptors. The number and type of thyroid receptor available varies by tissue. Two separate genes encode thyroid hormone receptors, TRHA and TRHB. TRHA produces six isoforms. All but 1, TRα1, lack a T3-binding domain and a DNA binding domain. The purpose of the short protein isoforms in thyroid hormone function is unclear. The THAB gene encodes fully functional receptors TRβ1 and TRβ2.

Thyroid hormone nuclear receptor activity in a target cell, Public Domain/Wikimedia Commons

Thyroid hormone receptor may bind to DNA as a monomer (one thyroid receptor), a homodimer (two thyroid receptors bound together) or a hetero-dimer (one thyroid receptor plus a retinoid X receptor). The heterodimer with the retinoid X receptor is the major functional form of the thyroid hormone receptor.

The active form of thyroid hormone at nuclear receptors is T3. Iodine must be removed from T4 converting it to T3 for receptor binding to occur. There are 3 forms of the de-iodination enzymes within thyroid hormone target cells. These enzymes, depending upon their location and activity, allow thyroid hormone function to be regulated deferentially throughout the body.

Thyroid hormone regulation at the cellular level may take place at plasma membrane uptake, at enzymatic removal of iodine from T4 and T3, and in the nucleus depending upon the type of receptor available.

Thyroid hormone negative feedback

The hypothalamus-pituitary-thyroid feedback loop is a negative feedback process that regulates synthesis and release of thyroid hormone from the gland. The simplest view of thyroid hormone feedback is presented in this image.

Thyroid hormone negative feedback system, Public Domain, Wikimedia Commons

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