Before we talk about thyroid hormones, it is important to remember what a hormone is.
The word hormones derives from the Greek hormao which means to set in motion, to stimulate, to excite. In fact, hormones are chemical messengers that transmit certain signals from one cell to another. The messages conveyed by the hormones contain all the instructions and orders necessary to regulate the metabolism and / or activity of the recipients. A cell is sensitive to the action of a hormone only if it has a specific receptor on its outer wall, that is a "mailbox" suitable for receiving the message.
Our thyroid can be compared to a real hormone factory, which influence the activity of a large part of the body. Another very popular comparison links the thyroid gland to a thermostat capable of accelerating or decreasing the body's metabolism depending on the conditions.
The thyroid is, therefore, an endocrine gland: "gland" because it produces and releases hormones, "endocrine" as it releases its secretion into the bloodstream.
As we saw in the lesson on thyroid anatomy, this butterfly-shaped gland with spread wings is made up of many "spherical pouches", called thyroid follicles. These follicles are the "functional unit of the thyroid gland and act as both a" factory " , which serves as a "warehouse" for thyroid hormones.
In particular, the follicles produce two very important hormones, thyroxine (more simply called T4) and triiodothyronine (or T3). These hormones are responsible for the proper functioning of many organs and body tissues. Their multiple functions will be explored in an upcoming video, while in this presentation we will focus on the mechanisms that regulate their production and secretion.
Thyroid hormones are produced in response to the stimulation of another hormone, the so-called TSH or thyrotropic hormone, produced and secreted by the anterior pituitary. This tiny gland located at the base of the skull secretes TSH to directly influence the activity of the thyroid. In turn, the release of TSH by the pituitary is controlled by another hormone, the TRH produced and secreted by the hypothalamus.
Let's take a step back to understand better. TSH is secreted by the anterior pituitary, a gland located at the base of the brain, and acts on follicular cells (or thyrocytes) promoting the production and release of T3 and T4 into the bloodstream. The resulting increase in thyroid hormones in the bloodstream has an inhibitory effect on both TSH and TRH release. This mechanism is called negative feedback and has the purpose of keeping thyroid hormones within stable, physiological levels, which adapt to the different conditions of the organism. The cold, for example, is picked up by the thermoregulatory center of the hypothalamus, which responds by secreting TRH. This hormone stimulates the pituitary gland to secrete TSH, which triggers the order to secrete thyroid hormones. At this point T3 and T4 act by raising the basal metabolism, therefore the body heating. However, it is important to avoid overheating of the body and it is for this reason that the increase of these hormones in circulation turns off the secretion of TRH and TSH.
Our whole body works with mechanisms of this type, since it is important to maintain homeostasis, ie the balance between the various bodily functions.
The measurement of TSH in the blood is therefore very useful for diagnostic purposes: little TSH means that the pituitary is trying to put the reins on an overactive thyroid; a lot of TSH instead means hypothyroidism: by increasing the amount of TSH in the circulation, the pituitary gland tries to convince the thyroid to produce more hormone.
Some elements are essential for the synthesis of thyroid hormones: iodine, the amino acid tyrosine and the enzyme thyroperoxidase (TPO).
Iodine is essential for the proper functioning of the thyroid, as it is present in the chemical structure of both thyroid hormones. Furthermore, it plays a decisive role in controlling their production and release in the bloodstream. For this reason, it is very important to ensure a sufficient intake of iodine with food; sea fish, crustaceans and, of course, iodized salt, essential to combat iodine deficiency, also very widespread in Italy, are rich in it. An insufficient intake of iodine leads to impaired synthesis and reduced concentrations of thyroid hormones. This T3 and T4 deficiency can cause various clinical manifestations. The best known consequence is goiter, that is the enlargement of the thyroid, and at this point we should understand why it arises. We have in fact seen how low levels of thyroid hormones stimulate the release of TRH and TSH; however, if there is not enough iodine, the levels of T3 and T4 continue to remain low, the stimulation of TSH continues to be high and the overstimulated thyroid enlarges giving rise to goiter.
In the colloid, which is present inside the cavity of the thyroid follicles, in addition to the iodine deposited in the form of iodide ion, there are also enzymes for the synthesis of T3 and T4 and thyroglobulin (Tg), which acts as a precursor for Thyroid hormones Thyroxine and triiodiothyronine derive from the amino acid tyrosine and thyroglobulin (Tg) supplies the tyrosine residues necessary for this synthesis.All components for the production of thyroid hormones are therefore stored in the colloid.
The phases of synthesis begin with the intervention of the thyroperoxidase enzyme, which catalyzes the iodination reaction of tyrosine. In practice, iodine is bound to the tyrosine residues of thyroglobulin, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). As the name suggests, monoiodotyrosine contains only one iodine atom, while diiodotyrosine contains two.
MIT and DIT are nothing more than precursors of thyroid hormones: in fact, T4 derives from the condensation reaction between two molecules of DIT, while T3 is obtained from the condensation of one molecule of MIT and one of DIT.
The thyroid hormones thus formed are bound to thyroglobulin supports and can be stored in the colloid for months after their synthesis. Curiously, in fact, the thyroid is the only endocrine gland that has the ability to accumulate hormones in the extracellular area, before they are released. When the TSH binding stimulates the endocytosis of the thyroglobulin-thyroid hormone complex in the follicular cells, the thyroglobulin support is degraded by enzymes, while the thyroid hormones are released into the cells, therefore into the bloodstream.
Since thyroid hormones are fat-soluble, once secreted into the blood they are transported by plasma proteins, such as thyroxine-binding globulin (or TBG), transthyretin (or TTR) and albumin. Only a minimal amount, however, called FT4 and FT3 (where F, stands for free) remains in free form and it is this small amount that represents the biologically active fraction of the hormones.
The circulating thyroid hormones are mainly represented by thyroxine T4. Most of the plasma T3 is in fact obtained from the deiodation of T4 in peripheral tissues; in practice, an iodine atom is removed from T4 to obtain T3.
It is important to remember that, despite being secreted in lower quantities than thyroxine, T3 is the most active form at the cellular level, responsible for most of the physiological effects.
Once the thyroid hormones reach their destination, they are able to cross the plasma membrane to bind to their receptor (the mailbox), present within the target cells. The specific receptors for thyroid hormones, in fact, are found in the nucleus, where they can interact with DNA to regulate the expression of various genes.
In addition to thyroid hormones, the thyroid also produces calcitonin, which is involved in the regulation of calcium metabolism. The hormone is synthesized and secreted by parafollicular cells or C cells in response to hypercalcemia, that is, an excess of calcium in the blood. In similar conditions, calcitonin lowers the blood concentration of calcium favoring its deposit in the bone and favoring its excretion by the kidney. The antagonistic action is carried out by the parathyroid hormone, the hormone secreted by the parathyroid glands.
