Thyroid Hormones

Question 1

What is the anatomy of the thyroid gland?

Answer 1

It is located inferior to the larynx, the two lobes are connected by the isthmus

Question 2

What do the thyroid follicles produce?

Answer 2

The thyroid hormones:
- thyroixine or tetraiodothyronine (T4)
- triidothyronine (T3)

Question 3

What do the thyroid hormones do?

Answer 3

They increase basal metabolic rate (BMR), stimulate protein synthesis, increase use of glucose and fatty acids for ATP production.

Question 4

What do the parafollicular cells or C cells produce?

Answer 4

The produce calcitonin.

Question 5

What does calcitonin do?

Answer 5

It lowers blood Ca2+ by inhibiting bone resorption.

Question 6

How is thyroid hormone synthesized?

Answer 6

The thyroid gland is made up of individual follicles that are ~1cm in diameter. These follicles are made up of cuboidal epithelial cells in a single layer around a lumen.The follicular cells synthesize a protein called thyroglobulin.

Question 7

What is thyroglobulin?

Answer 7

It is the substrate for tyrosine iodination and the synthesis of thyroid hormones. It is release via exocytosis into the colloid space.

Question 8

What is the process of thyroid hormone synthesis?

Answer 8

A. Dietary iodine is rapidly absorbed and circulates as iodine.

B. Follicular cells in the thyroid gland possess an active iodine trap that acquires and concentrates iodide from the circulating blood. Iodide is transported into the cell against the electrochemical gradient (more than 50mV) by a Na+=I–symport. The iodied pump is linked to a N+=K+=pump, which requires energy in the form of ATP. In the follicular cell, iodide passes down the electrochemical gradients through the apical membrane and into the follicular colloid (stored thyroglobulin)

C. The rough endoplasmic reticulum synthesizes a large storage molecule called thyroglobulin. Iodide-free thyroglobulin is transported in vesicles to the apical membrane, where they fuse with the membrane and finally release thyroglobulin at the apical membrane.

D. At the apical membrane the oxidized iodide is attached to the tyrosine units (l-tyrosine) in thyroglobulin at one or two positions, forming the hormone precursors mono-iodotyrosine (MIT), and di-iodotyrosine (DIT), respectively.

E. Each thyroglobuline molecule contains up to 4 residues of T4 and zero in one T3. Thyroglobulin is retrived back into the follifular cell as colloid droplets by pinocytosis. Pseudopods engulf a pocket of colloid. These colloid droplets pass towards the basal membrane and fuse with lysosomes forming phagolysosomes.

F. Lysosomes break the binding between thyroglobulin and T4 (or T3). Large quantities of T4 are released to the capillary blood. Only minor quantities of T3 are secreted from the thyroid gland.

G. TSH stimulates almost all processes involved in thyroid hormone synthesis and secretion.

Question 9

How is TSH regulated?

Answer 9

• By the hypothalamic releasing hormone, TRH (TSH-releasing hormone) aka Thyrotropin.
• The thyroid hormones feedback to inhibit both TRH and TSH.
• The hypothalamus can also be stimulated by certain types of stress to activate this system.
• Low skin temperature stimulates the release of TRH from the hypothalamus.
• Stress inhibits TSH secretion
• Thyroid gland is also innervated by sympathetic nervous system - stimulates short term alteration in thyroid hormone secretion.
• TSH stimulation increases synthetic machinery to make thyroid hormones (it increases the Rough ER, Golgi in follicular cells, this causes the cells to become columnar in shape and the lumen becomes smaller)
• TSH acts via GPCR - increases cAMP
• cAMP analogs stimulate follicular cells the same as TSH
• Oxygen consumption increases in follicular cells in response to TSH
• TSH stimulates rapid pinocytosis of TG into follicular cells
• There is more T4 made than T3 (about 50 times more in serum)

Question 10

What do deiodinases do?

Answer 10

The convert T4 into T3 at the levels of target tissues.

Question 11

How are thyroid hormones transported in the blood?

Answer 11

They behave like steroid hormones and are insoluble in blood. As a result, they are carried by carrier proteins (such as transthyretin and thyroxine binding globulin. 70% is bound to TBG, 20% to transthyretin and 5-10% bound to albumin.

Question 12

What are the target tissues of thyroid hormones?

Answer 12

They act on the liver, kidneys, heart, nervous system and skeletal muscle to increase the sensitivity of these tissues to epinephrine (via increases in adrenergic receptors). They also stimulate cellular respiration, oxygen consumption and metabolic rate, resulting in increased heat production (thermogenesis) by increasing the activity of the Na+/K+ATPase.

Question 13

What are the effects of thyroid hormones in the heart?

Answer 13

They have a permissive effect on catecholamines, they increase the expression of beta-receptors to increase heart rate, stroke volume, cardiac output, and contractility.

Question 14

What are the effects of thyroid hormones in the lungs?

Answer 14

They stimulate the respirator centers and lead to increased oxygenation because of increased perfusion.

Question 15

What causes congenital hypothyroidism?

Answer 15

It can result from either incomplete formation of the thyroid gland or the inability to synthesize thyroid hormones. This can lead to cretinism.

Question 16

What happens in hypothyroid patients?

Answer 16

Growth hormone secretion is diminished, and both GH and Thyroid hormone must be added to reverse.

Question 17

What else can cause hypothyroidism?

Answer 17

It can occur later in development due to a lack of iodine in the diet. This is because it cannot trap the iodine in the follicular cells meaning it is unable to produce thyroid hormone. Without the feedback loop TSH will increase.

Question 18

What happens when thyroid hormones split hyaluronic acid in developing tissues?

Answer 18

It can lead to a decrease in proliferation and stimulating differentiation.

Question 19

How do thyroid hormones regulate mammary gland development?

Answer 19

They act together with prolactin.

Question 20

What are thyroid hormones necessary for?

Answer 20

They are needed for normal neural development.
(Unlike for general body growth, neural deficits due to hypothyroidism are permanent.)

Question 21

What causes a goiter?

Answer 21

The inability to synthesize thyroid hormones.

Question 22

What is hyperthyroidism?

Answer 22

Also known as Graves disease, it is the result of too much thyroid hormone being release and results in exophthalmos (protruding eyes), increased sweating difficulty sleeping and increased appetite, weight loss and many other symptoms.

Question 23

What is hypothyroidism?

Answer 23

It results from inadequate release of thyroid hormones. This can be primary hypothyroidism from a disease of the thyroid gland, or secondary from failure of the pituitary gland to secrete TSH. It causes lowered metabolism, the patient feels cold, there is a loss of appetite and many other symptoms.

Question 24

How can you distinguish between primary and secondary hypothyroidism?

Answer 24

• Measure the concentration of TSH in the blood.
• If the problem is with the thyroid gland you would expect to find high levels of TSH.

Question 25

What is the thyroid hormone mechanism of action?

Answer 25

Thyroid hormone in the form of T3, acts by modifying gene transcription in virtually all tissues to alter rates of protein synthesis and substrate turnover.

Question 26

What is plasma membrane integrin avB3?

Answer 26

It is a cell surface receptor for thyroid hormone at which nongenomic actions are initiated.