Thyroid hormones are hormones that are produced by the thyroid gland. These hormones include thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid hormones regulate metabolism, heat production, protein synthesis, and many other body functions, thyroid disorders can have severe and widespread consequences. Calcitonin does not affect the metabolic turnover, but interferes with the metabolism of calcium (and phosphate) ions, which are responsible (among other functions) for the stability of membrane potential. 

The major form of thyroid hormone in the blood is T4, which has a longer half-life than T3. T4 is converted to the active T3 (three to four times more potent than T4) within cells by enzymes called deiodinases. In humans, the ratio of T4 to T3 released into the blood is between 14:1 and 20:1. 

T4 and T3 are tyrosine-based hormones that are primarily responsible for regulation of metabolism. They boost basal metabolic rate of proteins, fats and carbohydrates as well as vitamins. Thyroid hormones also affect the dilation of blood vessels, which in turn affects the rate at which heat can escape the body. The more dilated blood vessels are, the faster heat can escape. One suffering from hyperthyroidism (an overactive thyroid) will experience a fever; conversely, one suffering from hypothyroidism (a less active thyroid) will suffer from a decrease in body temperature.

When levels of T4 (Pic. 1; Pic. 2) and T3 (Pic. 3; Pic. 4) hormones are excessive, this effect accelerates the heart rate, strengthens the heartbeat, and increases blood pressure. Adequate levels of thyroid hormones are also required for protein synthesis and for fetal and childhood tissue development and growth. Thyroid hormones play a particularly crucial role in brain maturation during fetal development. They are especially critical for normal development of the nervous system both in utero and in early childhood, and they continue to support neurological function in adults. Cells of the developing brain are a major target for T3 and T4. 

The thyroid gland also secretes a hormone called calcitonin (Pic. 5) that is produced by the parafollicular cells (also called C cells) that stud the tissue between distinct follicles. It appears to have a function in decreasing blood calcium concentrations by:

  • inhibiting the activity of osteoclasts (bone cells that release calcium into the circulation by degrading bone matrix)
  • increasing osteoblastic activity (cells that synthesize bone)
  • decreasing calcium absorption in the intestines
  • increasing calcium loss in the urine

However, these functions are usually not significant in maintaining calcium homeostasis, so the importance of calcitonin is not entirely understood. Pharmaceutical preparations of calcitonin are sometimes prescribed to reduce osteoclast activity in people with osteoporosis and to reduce the degradation of cartilage in people with osteoarthritis.

Thyroid hormones have also a complex interrelationship with reproductive hormones, and deficiencies can influence libido, fertility, and other aspects of reproductive function. 

Synthesis and release of thyroid hormones (Pic. 6)

T3 and T4 are partially composed of iodine. T4 is produced by attaching iodine atoms to the ring structures of tyrosine molecules and contains four iodine atoms. T3 is identical to T4, but it has one less iodine atom per molecule.

In the bloodstream, less than 1% of the circulating T3 and T4 remains unbound. This free T3 and T4 can cross the lipid bilayer of cell membranes and be taken up by cells. The remaining 99% of circulating T3 and T4 is bound to specialized transport proteins called thyroxine-binding globulins (TBGs), to albumin, or to other plasma proteins. This “packaging” prevents their free diffusion into body cells. When blood levels of T3 and T4 begin to decline, bound T3 and T4 are released from these plasma proteins and readily cross the membrane of target cells. T3 is more potent than T4, and many cells convert T4 to T3 through the removal of an iodine atom.

Calcitonin is synthetized from a prohormone (precursor of a hormone) which is the product of the CALC1 (CALCA) gene. By an alternative splicing of that gene another peptide is formed – termed CGRP (calcitonin gene related peptide). 

Regulation of thyroid hormones synthesis

The release of T3 and T4 from the thyroid gland is regulated by thyroid-stimulating hormone (TSH). Low blood levels of T3 and T4 stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus, which triggers secretion of TSH from the anterior pituitary. In turn, TSH stimulates the thyroid gland to secrete T3 and T4. The levels of TRH, TSH, T3, and T4 are regulated by a negative feedback system (Pic. 7) in which increasing levels of T3 and T4 decrease the production and secretion of TSH.

If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. A lack of thyroid hormone will lead to decreased negative feedback on the pituitary, which in turn, will lead to increased production of TSH, which causes the thyroid to enlarge (goiter). This enlarged endemic colloid goiter has the effect of increasing the thyroid's ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone.

The secretion of calcitonin is increased during hypercalcemia, a state of increased blood calcium levels. Secretion of calcitonin is also stimulated by gastrin or/and pentagastrin (hormones that stimulate production of gastric acid).

Impact on fertility

Hypothyroidism may affect fertility through anovulatory cycles (no ovulation), luteal phases problems (fertilized egg can´t implant), high prolactin levels (irregular or absent ovulation), hormonal dysbalance (progesterone deficiency, high estrogen level).

Hyperthyroidism may cause low sperm count in men or irregular menstruation in women. 

Calcitonin was found in human seminal plasma at concentracions higher than in blood plasma. It is important for stimulating of capacitation and fertilizing ability in uncapatitated sperm. On the other hand, salmon calcitonin used for osteoporosis treatment has negative impact on human sperm motility. Calcitonin level is increased during pregnancy and lactation because of the demand for transfer of maternal calcium to the fetus/infant.

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The Thyroid Gland ―sourced from OpenStax College licensed under CC BY 4.0
Hormones ―sourced from OpenStax College licensed under CC BY 4.0
Thyroid-stimulating hormone ―sourced from Wikipedia licensed under CC BY-SA 3.0
Action of Thyroid Hormones ―sourced from Boundless licensed under CC BY-SA 4.0
Thyroid hormones ―sourced from Wikipedia licensed under CC BY-SA 3.0
Thyroid function tests ―sourced from Wikipedia licensed under CC BY-SA 3.0
Calcitonin ―sourced from Wikipedia licensed under CC BY-SA 3.0
Thyroid hormones ―by Maryníková, created for licensed under CC BY-SA 4.0
Thyroid hormone synthesis ―by Häggström licensed under CC0 1.0
Thyroid system ―by Häggström licensed under CC0 1.0
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