Thyroid Hormones and Thyroid-Stimulating Hormone

What are the thyroid hormones?

There are two major hormones secreted by the thyroid glandthyroxine (T4) and triiodothyronine (T3). The thyroid gland secretes more thyroxine (T4) than triiodothyronine (T3) but most T4 is eventually converted into T3. Although T3 is secreted in significantly smaller quantities, it is about four times as potent as T4.

The thyroid hormones are best known for regulating the metabolism of the body although it has several other effects on the different tissues of the body which become evident when there is an excess or deficiency of these hormones. Most of the secretion of the thyroid hormones are regulated by another hormone known as the thyroid-stimulating hormone (TSH), which is secreted from the pituitary gland, particularly the anterior pituitary.

Thyroid Hormones Production

Iodine is required to synthesize thyroid hormones and is ingested in the form of iodides. Most of the iodides that absorb into the blood stream from the gut are excreted by the kidneys but small quantities enter the thyroid cells to manufacture the thyroid hormones. The iodide is pulled inside the thyroid cell (iodide trapping) where it is concentrated to about 30 times the concentration of the blood iodide. The iodide is then oxidized into iodine by the enzyme perioxidase.

The thyroid cells produce a protein known as thyroglobulin which it secretes into the thyroid follicles. When these thyroglobulins, specifically the tyrosine amino acid in the thyroglobulin molecule, combine with iodine, it forms the thyroid hormones thyroxine (T4) and triiodothyronine (T4). The process of binding thyroglobulin with iodine is known as organification and catalyzed by the enzyme iodinase.

The combination of tyrosine and iodine form forms monoiodotyrosine and then diiodotyrosine. Thyroxine (T4) is formed by the binding of these diiodotyrosine molecules. If one monoiodotyrosine molecule combines with diiodotyrosine molecule, triiodothyronine (T3) is formed. Not all the iodinated tyrosine molecules on the thyroglobulin molecule become the thyroid hormones T4 and T3. Eventually each thyroglobilin molecule contains tens of thyroxine molecule and a few triiodothyronine molecules and stored in the follicles of the thyroid gland.

Thyroid Hormones Secretion

When the thyroid hormones are required by the body, it has to be cleaved from the thyroglobulin molecules into the follicles of the thyroid gland. This is achieved by the action of proteases released by the thyroid cells into the follicles. Any iodated tyrosine molecules bound to the thyroid molecule are also recycled at this point to possibly become thyroid hormones in the future.

Most of the thyroid hormone released from the thyroid gland is thyroxine (T4). Both the T4 and T3 that enter the blood stream bind to blood proteins in order to be transported through the circulatory system. This includes blood proteins like albumin and thyroxine-binding globulin. Over a period of several days, these protein-bound thyroid hormones are slowly released to enter the various cells of the body. Once the thyroid hormones enter a cell, it binds with proteins within the cell and stored for later use over days or even weeks. The delay for the use of the thyroid hormones by the cells is known as the latency period. Before being used, most of the thyroxine (T4) is converted to triiodothyronine (T3) by the removal of one iodide.

Thyroid Hormones Functions

The thyroid hormones are known to increase cellular metabolism. This a result of numerous effects on the various tissues and is not just a single process.

The thyroid hormones have the following effects that contribute to metabolic activity :

  • increases protein synthesis within the cell by activating large number of genes
  • increases the size and number of mitochondria which raises energy production
  • increases glucose metabolism by promoting uptake of glucose into the cells from the blood stream
  • promotes carbohydrate absorption from the gut and glycolysis and gluconeogenesis
  • promotes the release of lipids from fat tissue which can be used for energy production

Other effects of thyroid hormones include :

  • decreases the lipids in the blood (cholesterol, phospholipids, triglycerides)
  • decreases the body fat concentration and body weight
  • increases the heart rate and breathing¬† rate
  • increases cardiac output and blood flow through the body
  • increases appetite, digestion of foods and absorption of nutrients

The other effects of thyroid hormones can be identified by abnormalities in the levels of thyroid hormones. An excess or deficiency of the thyroid hormones can affect :

  • growth
  • sleep
  • gastrointestinal motility¬† (constipation or diarrhea)
  • sexual function (men and women)
  • menstrual cycle (women)
  • muscle activity
  • activity of other endocrine glands

Thyroid Hormones Control

The level of thyroid hormones, thyroxine and triiodothyronine, need to maintained within a normal range to ensure proper functioning of most systems of the body. An excess or deficiency will affect a host of bodily processes, hamper daily functioning and even lead to life-threatening complications over time. The main regulating factor for thyroid hormone secretion is the anterior pituitary hormone known as thyroid-stimulating hormone (TSH) or thyrotropin.

Thyroid-Stimulating Hormone (TSH)

When appropriately stimulated, the pituitary gland releases TSH which increases the secretion of both thyroxine (T4) and triiodothyronine (T3) from the thyroid gland. At the same time it also accelerates iodide trapping, organification and causes structural changes of the thyroid cells and thyroid follicles to facilitate the synthesis of more thyroid hormones. TSH is able to mediate these various effects of the thyroid gland by activating cyclic adenosine monophosphate (cAMP) within the cell. Cyclic adenosine monophosphate in turn triggers the various process described above, thereby acting as secondary messenger for TSH.

Thyrotropin-Releasing Hormone (TRH)

A feedback mechanism involving the hypothalamus controls the levels of thyroid hormones in circulation by regulating the secretion of TSH from the pituitary gland. This communication between the hypothalamus and pituitary gland is medicated by thyrotropin-releasing hormone (TRH).

When the level of circulating thyroid hormones drop too low, the hypothalamus secretes TRH which then travels via the hypothalamic-hypophysial portal blood to the pituitary gland. By acting on the TSH-secreting cells of the pituitary gland, TSH is synthesized and released into the blood stream.An excess of thyroid hormones in the blood stream decreases TRH and TSH secretion and therefore the release of thyroid hormones from the thyroid gland.

However, low levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) are not the only triggers for TRH and indirectly TSH release. Cold and emotions also affect TRH secretion by the hypothalamus.

In a cold environment, the temperature regulating center in the hypothalamus also increases TRH secretion. This in turn promotes the secretion of TSH and the release of thyroid hormones. These effects increase the basal metabolic rate thereby increasing the body temperature. Emotion, like excitement and anxiety, have the opposite effect on the secretion of thyroid hormones. Emotions stimulate the sympathetic nervous system which in turn increases activity throughout the body and therefore raises body temperature. This decreases TRH and TSH secretion which lowers thyroid hormone secretion and ultimately the basal metabolic rate.

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