17.8 Thyroid Gland

What is the largest structure in the body entirely devoted to endocrine activities?

Thyroid gland

What hormones does the thyroid release?

Thyroid hormone and calcitonin.

Thyroid gland (anatomy)

A butterfly-shaped gland located immediately inferior to the thyroid cartilage of the larynx (voice box) and anterior to the trachea. This gland is composed of left and right lobes, which are connected at the anterior midline by a narrow isthmus.

How are the left and right lobes connected?

By a narrow isthmus

Both lobes of the thyroid gland are…

highly vascularized, giving the gland an intense reddish coloration.

What is the thyroid gland enclosed of?

Within a connective tissue capsule.

The thyroid gland at the histologic level…

composed primarily of numerous microscopic, spherical structures called thyroid follicles.

The wall of each follicle is formed by simple cubodial epithelial cells, called follicular cells, which surround a central lumen. The lumen (internal space) of each thyroid follicle houses a viscous, protein-rich fluid termed colloid.

The follicular cells produce and release thyroid hormone (TH) by first synthesizing a glycoprotein called thyroglobulin(TGB) and secreting it by exocytosis into the colloid-filled lumen.

In brief, iodine molecules must be combined with the thyroglobulin in the colloid to produce thyroid hormone precursors, which are TGB molecules that contain immature thyroid hormone (pre-T3 and pre-T4) within their structure.

The TGB molecules with the attached pre-T3 and pre-T4 are stored in the colloid until the secretion of thyroid hormone is needed.

When the thyroid gland is stimulated to secrete thyroid hormone….

some of the colloid with thyroid hormone precursors is internalized by endocytosis into a follicular cell. It is transported to a lysosome, where an enzyme releases the immature thyroid hormone molecules from the TGB molecules in preparation for secretion of T3 and T4 from the follicular cells. The details of thyroid hormone synthesis, storage, and release are described and illustrated in L figure 17.16. Parafollicular (par'ă'fo'lik'yu'lar; para = alongside, near) cells, also known as C-cells, are the less numerous endocrine cells in the thyroid gland, and are located around the follicular cells (L figure 17.15b).

Parafollicular cells synthesize and release the hormone calcitonin,

What regulates the release of thyroid-stimulating hormone from the anterior pituitary and subsequent release of thyroid hormone from the thyroid gland?

The hypothalamus.

Steps in the regulation of Thyroid Hormone Release.

#1:The stimuli that are monitored by the hypothalamus for controlling metabolism are described shortly.

2. The stimuli are detected by the hypothalamus, which serves as the receptor.

3. In response to the various stimuli, the hypothalamus, serving also as the control center, releases thyrotropin-releasing hormone (TRH) int the hypothalamo-hypophyseal portal system.

4. The anterior pituitary, in response to TRH, releases thyroid-stimulating hormone (TSH).

5. TSH stimulates the thyroid gland to release thyroid hormone (TH). TH has two forms-trüodothyronine (T3) and thyroxine (T4)-which
   are released into the blood of the general circulation. Tz and T4, which are lipid-soluble molecules (see section 17.3a) are transported within the blood by transport proteins (e.g., thyroxine-binding globulin [TBG], albumin). At any given time, a small percentage of T3 and T4 becomes unbound from the transport proteins and can then exit from the blood.

6. Thyroid hormone stimulates targets cells(effectors) as described shortly.

7. The net result is an increased metabolic rate and release of nutrients into the blood to supply the energy required for the higher metabolism.

8. Increased blood levels of TH inhibit both the release of additional TRH from the hypothalamus and TSH from the anterior pituitary. Thus, both TRH and TSH release are regulated by negative feedback.

What is the most significant stimulus for regulating the release of TRH

A change in blood levels of thyroid hormone.

Decrease=additional TRH is released

Increase=less TRH is released.

This functions to maintain blood levels of thyroid hormone around an individual’s set point.

An individual’s set point for blood levels of thyroid hormone is…

• Genetically determined

• influenced by changes within the body.

• altered by environmental factors.

Cold weather, pregnancy, high altitude, hypoglycemia,

in children, decreased body temperature

Effects of thyroid hormone

• increases metabolism

• initiates the release of nutrients to supply the energy required for the higher metabolic rate.

TH is a lipid-soluble molecule, and was previously thought that it entered its target cells by the membrane transport mechanism of simple diffusion, it is now understood…

that TH is taken into target cells by specialized transport proteins. (At least 10 different proteins)

The iodine of the thyroid hormone prevents its passive movement across the plasma membrane.

Following its movement into a target cell, T4 is typically…

converted to T3, which is the most active form of TH. Most cells, however, have an enzyme to remove one iodine to convert T4 to T3. This increases a cell’s response to thyroid hormone because a much greater amount of T4(90%) than T3(10%) is produced and released from the thyroid gland.

The target cells of thyroid hormone include

• All cells

• Hepatocytes of the liver

• Adipocytes of adipose connective tissue

Thyroid hormones also influences functions of which systems?

Respiratory and cardiovascular

Thyroid hormone impact on all cells

Thyroid hormone increases the metabolic rate of all cells. TH specifically stimulates cells to increase their synthesis of sodium-potassium (Nat/Kt) pumps (see L section 4.3c). The action of these additional pumps, which are converting chemical energy of ATP to mechanical energy of the pump generates heat (as described by the second law of thermodynamics; see L' section 3.1c). The rise in temperature is referred to as the calorigenic (kă-

lor'i-jen'ik; calor = heat, genesis = production) effect.

Thus, thyroid hormone is significant in maintaining an individual's body temperature. Cells increase both

(a) amino acid uptake, which provides the structural building blocks for synthesizing new proteins (e.g., Nat/Kt pumps) and (b) glucose uptake, which provides the fuel for cellular respiration to generate additional ATP needed for the higher metabolic rate.

Thyroid hormone impact on the liver

TH stimulates other target cells to help meet the additional requirements for ATP. Hepatocytes of the liver are stimulated to increase both glycogenolysis (breakdown of glycogen into glucose) and gluconeogenesis (synthesis of glucose from noncarbohydrate sources), while glycogenesis (synthesis of glycogen from glucose) is inhibited, thus additional glucose is released into the blood.

Thyroid hormone impact on adipose connective tissue

Adipocytes of adipose connective tissue cells respond to TH by both increasing lipolysis (breakdown of triglycerides into glycerol and fatty acids) and decreasing lipogenesis (formation of triglycerides). As a result, both glycerol and fatty acids are released into blood as alternative nutrient molecules for cellular respiration. This saves blood glucose for the brain and is called the glucose-sparing effect.

Thyroid hormone impact on the Respiratory & Cardiovascular system

Respiration rate (breathing rate) increases in response to TH to meet the additional demands for oxygen, which is required for aerobic cellular respiration (see L' section 3.4e). Additionally, bloo flow through the cardiovascular system (heart and blood vessels) to the tissues increases to deliver more nutrients and oxygen. The specific effect of TH on the heart is indirect. TH stimulates the synthesis and display of additional plasma membrane cellular receptors (B-adrenergic receptors) of both the pacemaker (SA node) and cardiac muscle cells of the heart (i.e., TH causes up regulation of B-adrenergic receptors). These receptors bind epinephrine and norepinephrine (which stimulate the heart). The resulting increase in B-adrenergic receptors makes the heart more responsive to epinephrine and norepinephrine and heart rate and force of contraction increase, and greater blood flow results

Calcitonin is synthesized and released from…

The parafollicular cells of the thyroid gland.

The stimulus for calcitonin release from parafollicular cells

A high blood calcium level; it is also secreted in response to stress from exercise.

Calcitonin primarily inhibits…

osteoclast activity within bone tissue (which decreases the breakdown of bone tissue) and stimulates the kidneys to increase the loss of calcium in the urine.

The net effect of calcitonin

A reduction in blood calcium levels.

Calcitonin seems to have the greatest effect…

In the bones of growing children, where there is the greatest turnover of bone and does not seem to have a significant function in adults.