Thyroid Hormones: Physiology

Functional Thyroid Hormone

T3 (active) Three Iodine

Most are formed from the conversion of T4

Greater affinity for thyroid hormone receptors

makes 3-5 times more potent than T4

T4 (Inactive)

Four Iodine (Tyrosine)

Produced more than in the thyroid glands (90%)

Prohormone must be converted into T3 in peripheral tissues to exert

T4 to T3 by an enzyme called deiodinase in tissues like the liver and kidneys

What is colloid

Protein-rich center where thyroid hormone is synthesized and stored

What are follicular epithelial cells

Surround colloid and participate in almost all phases

What is thyroglobulin

A protein enriched in the thyroid gland

Source of TYROSINE AND THYROID HORMONE

Acts as a scaffold for thyroid hormone synthesis

Steps facilitated by TSH binding to the TSH receptor on follicle cell

1. Iodide is Co-transported with Sodium Ion

2. iodide Diffuses towards the follicle lumen

3. Iodide Transported to colloid and combines with tyrosines on thyroglobulin

4. The Iodinated Ring of One MIT/DIT is added to a DIT at another spot

5. Endocytosis of Thyroglobulin- Containing T3 and T4 molecules

6. Lysosomal enzymes cleave and release T3 and T4 from thyroglobulin

True or False: Hormones are inactive as long as they are bound to binding proteins

True

Iodine (iodinized salt, shrimp, seaweed)

Necessary for thyroid hormone production

Thyroid peroxidase

Important enzyme required for thyroid hormone production

Actions of Thyroid Hormone

Metabolic hormones, Permissive hormones, Growth Hormones

Thyroid Hormones

presents in the nuclei of most cells of the body organs

Brain and pituitary, heart, bone, adipose tissue, liver

Metabolic and Catorigenic Actions

High affinity T3 receptors are present in most of the cell body

T3 stimulates a very diverse array of metabolic activities in most tissues by:

Increases overall metabolic rate

Increases oxygen consumption and ATP hydrolysis

Leads to an increased thermogenesis

Permissive Hormone Action

Thyroid hormone dramatically increases the effect of epinephrine at a target cell; Due in large part to its ability to increase the number of target cell surface receptors of epinephrine

Growth and Development

Thyroid hormone acts closely with growth hormones (GH) for body growth and development

Important role in early brain structure development

Thyroid Gland Regulation and Function

TSH binds to its receptor in the thyroid gland

Stimulates all steps involved in thyroid hormone synthesis and release

Thyroid Gland

Stores iodine and thyroid hormone in colloid

Produces more T4 (inactive) than T3 (active)

Thyroid Hormone

Synthesis and release under negative feedback regulation by the HPT axis

T4 (prohormone) is converted to T3 (hormone)

Binds to nuclear receptors and modulates gene expression

Iodinate of Tryosines

Results from the formation of monoditryosine (MIT) and diiodotryosine (DIT) precursor for T3 and T4

One DIT + One MIT

T3

One DIT + One DIT

T4

Why does Iodine Matter

Iodine is the building block of thyroid hormones

Without enough iodine, thyroid can’t make enough T3 and T4, which leads to problems like an enlarged thyroid (goiter) or hypothyroidism (low hormone levels)

Negative Feedback Along the Hypopituitary Thyroid Axis

Begin: 1. Neural Inputs

2. Hypothalamus (TRH secretion)

3. Plasma TRH

4. Anterior Pituitary

5. Plasma TSH

6. Thyroid gland (T3, T4 secretion)

7. Plasma Thyroid Hormone

8. T4 converted to T3 (respond to increase T3)