L2: Thyroid Glands and Thyroid Hormones

Where are the thyroid glands located relative to the trachea?

two lobes on either side of the trachea, just below the larynx

What supplies blood to the thyroid lobes?

A branch of the common carotid artery.

What are the main structural components of the thyroid gland?

1. thyroid follicles

2. thyroid cells

3. C cells

what are thyroid follicles filled with?

colloid

What hormones are produced by thyroid cells?

Thyroxine (T4) and triiodothyronine (T3).

Which cells of the thyroid produce calcitonin?

C cells

What are the basic building blocks of thyroid hormones?

Tyrosine amino acid and iodine.

what type of hormon are thyroid hormones?

amine hormoens

what is the exception to thyroid hormones?

while they are amine hormones they behave like LIPID-SOLUBLE hormones

how is iodine obtained?

through the diet as it is not produced in the body

Where is iodine primarily absorbed in the digestive system?

In the duodenum

What is iodine trapping?

Active process when there is an uptake of iodine from blood into thyroid follicular cells via a symporter on the basolateral membrane of the thyroid gland

Which transporter concentrates iodine into thyroid cells?

Sodium-iodide symporter (NIS).

what is used by the symporter to pull iodine into the blood?

ATP

What is unique about the thyroid’s ability to concentrate iodine?

It is the only organ that actively concentrates iodine from the bloodstream

tyrosine

non-essential amino acid that can be obtained from diet or synthesized

why is both iodine and tyrosine essential in the thyroid?

necessary to make T3 and T4

What is the storage form of thyroid hormone precursors inside the thyroid follicle?

Thyroglobulin (TGB) within the colloid

How are iodinated tyrosine residues formed on thyroglobulin?

Iodination of tyrosine residues via iodination enzymes

iodine trapping

iodine is being pushed into the thyroid cell

TGB

• thyroglobulin

• large protein that is made from DNA within the thyroid cell

• will be pushed out of cell through secretory vesicles to enter colloid

what are the basic steps invoved in the synthesis of thyroid hormones in the thyroid cell?

1. iodine trapping

2. synthesis of TGB through DNA

3. oxidation of iodine via peroxidases and secreted into colloid

4. iodination of tyrosine via iodinases

5. coupling of T1 an T2 to form T3 and T4

6. pinocytosis and digestion of colloid to have T3 and T4 in lysosome of thyroid cell

7. Secretion of T3 and T4 back into the bloodstream

8. Transport hormones in blood (REQUIRE TRANSPORTER

what is happening in the pinocytosis step during synthesis of thyroid hormones in the thyroid cell?

apical membrane of cell engulfs the colloid with tyrosine and will start to chop it into T3 and T4 in the lysosome

t/f: thyroid hormones require a transporter when being transported in the blood

true

How are T3 and T4 released from the thyroid?

Lysosomal breakdown of iodinated thyroglobulin releases T3 and T4 to then be transported

Which hormone primarily stimulates the thyroid to produce hormones?

Thyroid-stimulating hormone (TSH) from the pituitary

What environmental factor can stimulate thyroid hormone production besides TSH?

Cold exposure and higher brain centers

Which thyroid hormone is produced in greater quantity by secretion?

T4 (about 93% of the produced hormone)

what will be secreted first from the hypothalamus when the animal is cold (stimulus)?

TRH which will then act on anterior pituitary

what does the anterior pituitary release when it has been stimulated by TRH?

TSH

how does TSH reach the thyroid gland?

systemic circulation

what does TSH in the thyroid gland stimulate?

follicular cells of the thyroid gland to release TH

what does TH stimulate when it has been released by thyroid gland?

stimulates target cells to increase metabolic activities to increase body temperature

what detects the increased body temperature in the animal and what will occur?

• hypothalamus

• secretion of TRH will by the hypothalamus will be stimulated

what inhibitory effects will TH have on the animal?

TRH receptors on thyrotropic cells will be blocked meaning that synthesis and release of TSH will be inhibited and TH production in thyroid will decrease

what is important to know about negative feedback in thyroid hormone regulation?

occurs at BOTH the hypothalamus and anterior pituitary level

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

1. stimulation of iodine uptake

2. stimulation of iodination of tyrosine

3. growth of thyroid cells

why do thyroid hormones bind to different proteins in the blood?

they have low solubility in plasma

Which plasma proteins bind thyroid hormones in circulation?

Thyroxine-binding globulin (TBG) and albumin

what thyroid hormone is the most active form?

T3

Why do bound thyroid hormones have longer half-lives?

Binding to plasma proteins protects them from degradation, extending their half-life

why is it important that bound thyroid hormones have longer half-lives?

the body will have a longer storage availability circulating in blood and have better storage of thyroid hormones in follicles

where is the storage occurring of thyroid hormones?

colloid and blood

What enzyme class converts T4 to the more active T3 in tissues?

Deiodinase enzymes

what is important to understand about T4 and deiodinases?

process is happening when T4 has entered and IS IN CELL

What is the functional significance of reverse T3 (rT3)?

An inactive metabolite that reflects T4 degradation; limited functional significance

Which thyroid hormone is more active, T3 or T4?

T3 is more bioactive than T4

What happens to T3 after entering the target cell (it has been already deionise from T4)?

1. T3 binds to nuclear receptor to activate gene transcription

2. new intracellular proteins form

3. actions of thyroid hormones can occur

What is the consequence of T3 binding to nuclear receptors?

Activation of gene transcription and synthesis of new intracellular proteins

What general cellular effect do thyroid hormones have on metabolism?

They increase the production INTRACELLULAR proteins, including metabolic enzymes

what does the non-genomic pathway act on?

mitochondria

How do thyroid hormones affect mitochondria?

They increase mitochondrial size and number, boosting metabolic capacity to form ATP

where is the receptor located for T3 and T4 on the cell and what occurs?

The receptor is located in the nucleus, where T3 and T4 regulate gene expression and protein formation

MCQ: what explains the long half-life of thyroid hormones?

binding to plasma proteins

What is the site of thyroid hormone storage prior to release?

Within thyroglobulin in the colloid.

what is produced by C cells and what is their function?

• Calcitonin

• helps regulate calcium

what are the main effects of thyroid hormones on metabolism?

1. increase size and amount of mitochondria

2. increase BMR

3. GENERATES HEAT

4. increase activity of sodium-potassium pump

5. increase amount of metabolic heat produced

how do thyroid hormones affect carbohydrate metabolism and what does this mean?

1. increases glucose absorption and uptake

2. increases glucose utilization

SUPPLY FUELS FOR ENERGY

how do thyroid hormones affect lipid metabolism and what does this mean?

1. stimulate lipolysis

2. increase bile secretion and fat absorption

3. lower blood cholesterol (relevance: hyperthyroidism)

SUPPLY FUELS FOR ENERGY

what is the effect of thyroid hormones on protein metabolism?

• normal growth dependent on hormones

• balance protein synthesis and degradation

• tissue growth and repair

• prevent excess breakdown of proteins

what does “protein anabolic” mean?

synthesis of proteins and increased rate of cell division

what does “protein catabolic” mean and why does this occur?

proteins being destroyed due to excess levels of thyroid hormones

what are the effects of thyroid hormones on the nervous system?

• essential for development of CNS during fetal and newborn period

• excitatory effect on CNS ( keeps CNS active)

• enhances response of sympathetic target tissues to increase receptors for both epinephrine and norepinephrine

what do thyroid hormones act on in the cardiovascular system?

Beta-1 adrenoreceptors

what is the effect of thyroid hormones on the cardiovascular system?

1. increases heart rate and contraction strength

2. indirectly increases blood flow (CO2)

inotropism

contraction strength of heart

chronotropism

heart rate

what is the effect of thyroid hormones on the respiratory system?

increase oxygen utilization and carbon dioxide production to effect respiration rate and depth

what is the effect of thyroid hormones on the GI tract?

1. increase appetite and food intake

2. increase motility and secretion

what happens to the GI tract if there is a lack of thyroid hormones?

constipation

how do thyroid hormones effect an animal’s skin and hair?

1. inhibit synthesis of hyaluronic acid, fibronectin, and collagen

2. proliferation of fibroblasts

3. downregulate apoptosis of keratinocytes

what are the steps of hair growth?

1. early anagen

2. late anagen

3. catagen

4. telogen

early anagen

The initial phase of the hair growth cycle, where hair follicles begin to produce new hair strands

what stimulates anagen?

1. TSH

2. T3

3. T4

what inhibits anagen?

1. glucocorticoids

2. estrogen

3. testosterone

4. substance P

5. nerve growth factor

what can cause prolongation of late anagen?

1. TSH

2. T3

3. T4

what can lead to premature catagen induction?

1. glucocorticoids

2. estrogen

3. substance P

4. nerve growth factor

catagen

hair growth has begun to slow down

what can lead to premature telogen induction?

1. glucocorticoids

2. estrogen

telogen

hair has stopped growing

kenogen

a state where hair is absent from the follicle after shedding, typically following telogen; hair growth can begin again after this

What happens if thyroid hormone production is chronically high—hyperthyroidism?

Overproduction of T3 and T4 leading to signs such as tachycardia, weight loss, heat intolerance

hyperthyroidism is mainly in what animal?

cats

hypothyroidism is mainly in what animal?

dogs

What happens if thyroid hormone production is chronically low—hypothyroidism?

Underproduction of T3 and T4 leading to signs such as obesity, lethargy, bradycardia.

MCQ: How does abnormal levels of thyroid hormones affect the normal physiology of metabolism in the body?

hypothyroidism decreases metabolic rate, leading to weight gain and cold intolerance

what are the main clinical signs of hyperthyroidism?

1. hyperactivity

2. mated hair or alopecia

3. weight loss

4. polyphagia

5. vomiting and diarrhea

what are the clinical signs of hyperactivity with hyperthyroidism?

1. increased metabolic rate

2. excess energy

3. heat intolerance

4. aggressive behavior

5. excessive grooming

why may cats have alopecia with hyperthyroidism?

thyroid hormones accelerate hair cycle leading to premature shedding

polyphagia

increased appetite due to increased calorie utilization in animal

when looking at the GI tract, why can thyroid hormones cause vomiting and diarrhea in cats with hyperthyroidism?

thyroid hormones can directly affect the chemoreceptor trigger zone in the medulla oblongota

What is a common cardiovascular sign of feline hyperthyroidism?

• Tachycardia and possible systolic murmurs due to increased beta-adrenergic receptors

• eventually will have ventricular hypertrophy

what respiratory alterations will occur in a cat with hyperthyroidism and why?

• panting and coughing during stress

• due to increased carbon dioxide and reduced respiratory muscles

what are the steps that lead to hypertension due to increased T3/T4 in cats with hyperthyroidism?

1. increased T3/T4

2. increased beta-1 adrenoreceptors in heart

3. tachycardia

4. hypertension

what are the steps that lead to heat intolerance due to increased T3?T4 in cats with hyperthyroidism?

1. increased T3/T4

2. increased metabolic rate

3. increased ATP

4. increased heat production

5. heat intolerance

what are the steps that lead to weight loss due to increased T3?T4 in cats with hyperthyroidism?

1. increased T3/T4

2. increased proteolysis

3. weight loss

what happens if you have insufficient thyroid hormones or TsH secretion during hypothyroidism?

1. decreased T4 and T3

2. decrease in krebs cycle and electron transport chain

3. decreased metabolic rate, ATP, and activity

4. metabolism and organ/tissue activity is slowed down

What is a common skin/hair sign of hypothyroidism in dogs?

1. Dry dull hair

2. alopecia

3. seborrhea

4. myxedema

5. sad face

6. thickening and darkening of skin

7. rat tail

why does myxedema occur in dogs with hypothyroidism?

excessive hyaluronic acid accumulates above the eyebrows leading to a sad face appearance in dog

why does hyperpigmentation occur in dogs with hypothyroidism?

epidermal hyperkeratosis and melanosis