Thyroid hormones

Definitions & Key takeaways

Thyroid hormones are hormones produced by the thyroid gland, which is located in the neck. The two thyroid hormones are thyroxine (T4) and triiodothyronine (T3); with T3 having the more active role in metabolic activities. Both thyroxine (T4) and triiodothyronine (T3) are produced and secreted by the thyroid gland in response to the thyroid-stimulating hormone which is secreted by the anterior pituitary lobe.

Thyroid hormones play a vital role in regulating metabolism and controlling the rate at which the body burns calories and uses energy. They also help to regulate body temperature, heart rate, and blood pressure, as well as growth and development in children.

Chapters:

Watch video only

Introduction0:00–1:04

Thyroid hormones are triiodothyronine or T3, and thyroxine, also called T4 or tetraiodothyronine. They’re two tyrosine-based iodine-containing hormones that help regulate our body’s metabolism.
T3 and T4 are produced by the thyroid gland, which is located in the neck and consists of two lobes that look like two thumbs hooked together in the shape of a “V”.
If we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells or thyrocytes, and are separated by a small amount of connective tissue.
Follicular cells are bipolar cells - with an apical side that surrounds a central cavity or lumen filled with the colloid, which is a fluid that contains the precursor hormone thyroglobulin.
Thyroglobulin is a large glycoprotein that is synthesized by the follicular cells and then it is secreted into the lumen of the follicle to be stored in the colloid.
The basolateral side of follicular cells is in contact with blood vessels. The basolateral membrane contains a sodium-iodide symporter, which pumps two sodium ions into the cell down their electrochemical gradient, in order to bring one iodide ion into the cell from blood.

Production1:04–2:26

Iodide is then pumped into the colloid through an ion transporter called pendrin, which exchanges iodide for chloride, since they’re both negatively charged.
Once iodide is in the colloid, it undergoes oxidation with the enzyme thyroperoxidase, which changes it into an iodine atom.
It’s then attached to tyrosine amino acid residues which are found throughout thyroglobulin. This process is called iodination.
Some tyrosine residues are bound by only one iodine, whereas others are bound by two iodine atoms, yielding monoiodotyrosine or MIT, and diiodotyrosine or DIT, respectively.
These molecules are then linked together by thyroperoxidase. Linking one MIT with one DIT creates T3, while linking two DIT molecules creates T4 - and both T3 and T4 remain bound to thyroglobulin.
You see - thyroglobulin basically serves as a peptide that stores these hormones on it in the colloid, until it’s ready to be used.
T4 is created in greater amounts than T3. When the follicular cells are ready to secrete T3 and T4, they endocytose the thyroglobulin into a vesicle which then fuses with the lysosome.

Secretion2:26–2:59

Here, thyroglobulin is cleaved by proteases, and T3 and T4 are released right into the bloodstream through the monocarboxylate or MCT transporter.
T3 is the highly active form with a half life of one to two days, while T4 is the less active form with a longer half life of six to eight days.

Control2:59–4:28

Production and secretion of thyroid hormones is under control of the hypothalamus-pituitary axis. The hypothalamus, which is located at the base of the brain, secretes thyrotropin releasing hormone, or ΤRH, into the hypothalamo- hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
In the anterior pituitary, TRH binds to a surface protein on a group of pituitary cells, called thyrotroph cells, and stimulates them to release the hormone thyrotropin, also called thyroid stimulating hormone or simply TSH, into the bloodstream.
TSH then travels to the thyroid gland, and binds to the TSH receptors located in the membrane of the follicular cells of the thyroid gland.
The TSH receptor is a seven pass transmembrane receptor, meaning that it’s a really long protein that has one end that sits outside the cell and binds TSH, then the snake-like protein dips in and out of the cell membrane seven times, and finally it ends on the inside of the cell.
The end of the protein within the cell activates intracellular proteins. When TSH binds to the TSH receptor, it goes on to promote every aspect of T3 and T4 production, including iodide pumping, thyroglobulin synthesis, iodination, and release of thyroid hormones into the bloodstream.

Release4:28–5:06

Once released from the thyroid gland, T3 and T4 enter the blood and bind to circulating plasma proteins - the most important one being thyroxine binding globulin or TBG, but they also bind to albumin and transthyretin.
Bound T3 and T4 acts like a reservoir of hormone that’s not biologically active. In fact, only a small amount of T3 and T4 will travel unbound in the blood - about 0.03% of T4 and 0.3% of T3 - and this fraction is biologically active, which means that this is what gets picked up by virtually every cell in the body.

Effects5:06–6:33

Once inside the cell, T­4 is mostly converted into T3 by the enzyme 5’- iodinase. T3 binds to thyroid hormone receptors which are within the cell’s nucleus, and these receptors regulate gene expression.
Normally, the thyroid hormone receptor, along with a corepressor molecule, is bound to DNA regions called thyroid hormone response elements, and that blocks gene transcription.
When T3 binds to its receptor, the corepressor molecule gets displaced, and a coactivator molecule attaches instead - allowing gene transcription to proceed.
T3 helps to speed up the basal metabolic rate, especially when we have to adapt to the environment. So as an example, exposure to cold weather stimulates the release T3 and T4, and they go on to increase body metabolism and heat production by burning up more energy in the form of sugars and fats.
Thyroid hormones help activate the sympathetic nervous system, which is responsible for the fight or flight response. This increases cardiac output, respiratory rate, and mental alertness.
Thyroid hormones are also involved in increasing sebaceous and sweat gland secretion, and promoting hair follicle growth.
They also have a very important developmental role, they work synergistically with growth hormone to promote long bone growth, and are necessary for normal brain development.

Feedback6:33–7:20

For all this to work properly, the levels of thyroid hormones have to stay within the normal range. And to do that, the body uses negative feedback, which means that high levels of thyroid hormones tell the hypothalamus and anterior pituitary gland to stop their secretion of TRH and TSH, respectively, lowering thyroid hormone secretion from the thyroid gland.
When thyroid hormones are low, the hypothalamus and anterior pituitary gland increase their secretion of TRH and TSH, respectively.
More TRH increase TSH production in the pituitary and the thyroid gland gets more stimulation to make thyroid hormones, and eventually, T3 and T4 levels go back up to the normal range again.

Review7:20–7:46

Alright, as a quick recap, thyroid hormones - so T3 and T4 - are produced by the thyroid gland under control of TSH, which in turn is released by the anterior pituitary under control of TRH released by the hypothalamus.
They mainly help speeding up our basal metabolism, but also stimulate the sympathetic nervous system, help regulate long bone growth, and are necessary for normal brain development.