HR Lesson 2: Thyroid Glands- Thyroid hormones

Structure of thyroid glands

Consist of 2 lobes, located on either side of the trachea, just below the larynx

Lobes are richly supplied with blood by a branch of the common carotid artery

Thyroid follicles are filled with…..

Colloid

What do thyroid cells produce?

Thyroxin (T4) and Tri-iodotyrosine (T3)

What do C cells produce?

Calcitonin

T4 and T3

The hormones produced by the thyroid glands, small amine hormones made up of tyrosine and iodine

Behave like lipid-soluble hormones

Where does iodine come from and how is it absorbed?

From the diet, and absorbed in the duodenum (90%) and into blood circulation

How is iodine taken up by the thyroid follicular cells?

From blood via an active process called “iodine trapping”

The thyroid is the only organ that does what?

Actively concentrates iodine from the bloodstream

How is iodine transported into thyroid cells?

By the sodium-iodine symporter (NIS)

Tyrosine

Non-essential amino acid that comes from the diet or is synthesized

What 2 components are necessary for the normal synthesis of thyroid hormones?

Tyrosine and Iodine

Synthesis of T3 and T4

1. Iodide uptake from blood via NIS

2. Synthesis and exocytosis of thyroglobulin (TGB) into the colloid

3. Iodide is oxidized via peroxidases into iodine and then secreted into the colloid

4. TGB tyrosine residues are iodinated via iodinases and formon the TGB an array of tyrosine residues with different degrees of iodination

5. The iodinated tyrosine residues form couples of T3 and T4 within the structure of TGB

6. Iodinated thyroglobulin is broken down in the thyroid cells by lysosomal enzymes

Thyroglobulin (TGB)

Amino acids including tyrosine

storage form and building block of T4 and T3

Thyroid hormone regulation

A stimulus (ie cold temperatures) triggers release of TRH from hypothalamus to the anterior pituitary which stimulates release of TSH to systemic circulation which stimulates release of TH to stimulate target cells to increase metabolic activities

How does TSH stimulate the thyroid gland to produce thyroid hormones?

Stimulation of iodide uptake

Stimulation of iodination of tyrosine

Growth of thyroid cells

Which thyroid hormone is more major?

T4 ~93%

T3 ~7%

Why do thyroid hormones have a longer half-life than unbound thyroid hormones?

Because T4 and T3 are bound in blood to plasma proteins

Body has a longer storage availability circulating in blood along with the storage of thyroid hormones in follicles

What plasma proteins do most T4 and T3 hormones bind to?

Thyroxine Binding Globulin (TBG) and Albumin (Alb)

How are clinical signs in the animal affected by longer storage availability and longer half life?

Clinical signs come much later if thyroid gland has a defect because of the large amounts of storage

Conversion of T4 into T3 within the target cell

Once in the vicinity of target cell, T4 and T3 unbind from transport proteins and enter the cell

Most tissues can convert T4 into T3 because T3 is more bioactive than T4

What happens to T4 that is not converted into T3?

Deiodinases convert T4 into reverseT3 which do not have any major functional significances and is inactive once degraded

Mechanism of action of T4 and T3

T4 is deionised into T3, T3 binds to nuclear receptors and to the DNA to activate gene transcription then is translated into hundreds of new intracellular proteins

What do the intracellular proteins do that are made by T3?

Most of the actions of thyroid hormones are the result of the proteins

Many of the new proteins synthesized are enzymes that control metabolic pathways

What are the main effects of thyroid hormones on metabolism?

Increase the size and number of mitochondria

Increase basal metabolic rate

Supplies and oxidizes fuels to generate heat

Increases the activity of the Na/K ATPase pump

Increases the amount of metabolic heat produced

What are the main functions of thyroid hormones on carbohydrate metabolism?

Increases glucose absorption and uptake

Increases glucose utilization

What are the main functions of thyroid hormones on lipid metabolism?

Stimulates lipolysis

Increases bile secretion and fat absorption

Lowers blood cholesterol

What are the main functions of thyroid hormones on protein metabolism?

Normal growth depends on thyroid hormones

Protein anabolic, increases the rate of cell division

In adults during excess, turns catabolic

Normal state of thyroid hormones in regards to protein metabolism

Helps maintain a balance between protein synthesis and degradation, ensuring adequate tissue growth and repair, while preventing excessive breakdown of proteins

What are the main functions of thyroid hormones on the nervous system?

Essential for the development of the CNS during fetal and newborn periods

Excitatory effects on the CNS

Enhances the responsiveness of sympathetic target tissues

What are the main functions of thyroid hormones on the cardiovascular system?

Increases heart rate (B1 adrenoreceptors: chronotropism)

Increases contraction strength (inotropism)

Indirectly increases blood flow (CO2)

Cardiac output increases

What are the main functions of thyroid hormones on the respiratory system?

Increase O2 utilization and CO2 production

Increase respiration rate and depth

What are the main functions of thyroid hormones on the gastrointestinal system?

Increases appetite and food intake

Increases motility and secretion

Lack of thyroid hormones can cause constipation

What are the main functions of thyroid hormones on skin and hair follicles?

Prolongs the duration of anagen

Inhibits the synthesis of hyaluronic acid, fibronectin, and collagen

Hyperthyroidism

Occurs when the thyroid gland overproduces thyroid hormones, resulting in excessive levels of T3 and T4

Hypothyroidism

Occurs when the thyroid gland produces insufficient amounts of thyroid hormones

Effects and clinical signs during hyperthyroidism

Hyperactivity, matted hair or alopecia, and weight loss, polyphagia (increased appetite), GI features (vomiting and diarrhea), cardiovascular (tachycardia), respiratory alterations (panting/coughing)

Effects and clinical signs during hypothyroidism

Obesity and lethargy (lack of energy, exercise intolerance), cardiovascular features (bradycardia due to decrease B1 receptors and decrease rate of calcium uptake by the sarcoplasmic reticulum), skin alterations (dry, dull hair, and alopecia), seborrhea, myxedema, hyperpigmentation

Main drug used for hyperthyroidism

Methimazole

How does methimazole work?

Blocks production pathways by providing a substrate for thyroxine peroxidase and decreases incorporation of iodide into tyrosine molecules

Main drug used for hypothyroidism

Levothyroxine

How does levothyroxine work?

Synthetic hormone (T4) that restores normal levels and reverses clinical signs