80. The thyroid hormones Flashcards
Thyroid hormones in general
Thyroid hormones act on every cell of the organism. There are HREs (hormone responsive elements) in the DNA of each cell.
These control the gene expression of various metabolic enzymes and structural proteins, depending on the intracellular concentration of thyroid hormone and other lipid soluble hormones from the steroid/retinal/D-hormone group.
The presence of thyroid hormone is important for normal development, especially development of the nervous system or mental functions.
Essential for the maintenance of normal metabolism and thermoregulation (not in reptiles, only body development).
Thyroid morphology
- Thyroid glands is a symmetrical, paired organ located in the cervical region. Its blood supply is intensive.
- Thyroid hormones cannot be passed through the placenta to the embryo, thats why it is developed in embryonic life.
- Its lumen is covered by a simple epithelium, the surface in microvilli. In the lumen the colloid matrix is rich in carbohydrates and proteins and serves as a hormone reserve.
- The colloid can maintain a normal level of thyroid hormones for several weeks, even though the novel hormone synthesis is lacking.
Inactive - flattened cells with the colloid relatively increased in size.
Deficiency symptoms
Young - Dwarfism, decrease fertilization, neural symptoms
Adult - Hair loss, matted fur, swollen CT, Neural functions are slowed down, body temperature also decreases.
Symptoms of overproducion
Thyroid hormone overdose or overproduction = (hyperthyroidism).
- Catabolic processes become emphasized.
- Burning of fat increases
- Protein and lipid stores of the body are decreased
- Decrease of body weight.
- Heart rate increase
- Increased irritability
Basedow’s syndrome (Graves’ disease)
General regulation
Controlled by feedback regulation, both long ( TRH synthesis) and short (TSH synthesis). Both the long and the short feedback regulation are inhibited by T3.
T3 is mostly derived from T4 (T4 becomes T3 in the tissue).
T4 is regulated by exogenous and endogenous factors.
The exogenous factors:
Photoperiod, feeding, temperature, stress and drugs.
The endogenous factors:
Genetic determination, physiological state, changes of hormone receptors and the activation ability of the peripheral cells.
Hormone synthesis
Synthesizes hormones and also stores them.
Iodide ions are transported into the thyroid cells from the bloodstream by an active pump, then iodide ions are converted to atomic iodine.
Thyroid hormones are located in the area of giant follicular proteins called thyroglobulin (TG).
Follicular cells degrade TG and secrete ready thyroid hormones into the circulation.
Hypophyseal TSH facilitates each step of hormone synthesis, except the release of hormones from cells
Hormone synthesis - Steps
- Iodine enters the gland by the active pumps.
- By the help of lysosomal peroxidase enzyme the iodine will be converted into atomic iodine.
- The atomic iodine makes either monoiodotyrosine (MIT) consisting of 1iodine or diiodotyrosine (DIT) consisting of 2iodine. The MIT or DIT will then bind to the TG (thyroglobulin).
2DIT will make one T4, while 1DIT + 1MIT will make either one T3 or rT3. - The epithelial cells synthesise the colloid TG, for the purpose of storing the hormones.
- Endocytosis of TG will be the first step of hormone release
- Only the T4 and T3 get into the bloodstream, while the other proteins will be degraded intracellularly.
- T4 and T3 will be secreted at the basal side of the cells by the help of passive diffusion.
Tyrosin
The primary molecule of thyroid hormone synthesis.
Thyroxine
Thyroid hormones are amino acid derivatives containing iodine atoms and built on a thyronine frame.
Common name = thyroxine (T4)
Triiodothyronine
Triiodothyronine is the active thyroid hormone, responsible for the biological effects of the thyroid gland
Reverse triiodothyronine
Reverse triiodothyronine, rT3, is an inactive form. It only
has a role in certain regulatory steps.
Hormone transport
Thyroid hormones are lipid soluble hormones, therefore binding proteins are needed to keep them dissolved in the water phase of the plasma.
- Thyroid- binding globulin (TBG)
- Thyroid-binding prealbumin (TBPA, or transthyrethin)
- T4 also binds to albumin.
- 0.02 % of T4 and 0.2 % of T3 dissociates from carrier proteins and it can be found in free forms in circulation. This form enters the tissues.
Most of T3 binds to TBG, a few bound to albumin in circulation. T3 does not bind to TBPA.
Deiodinases
Deiodinase is a peroxidase enzyme that is involved in the activation or deactivation of thyroid hormones.
Hormone effects
- effects on development
- regulation of metabolic rate (energy balance) of the organism.
- metabolism of the heart, skeletal muscles, liver and skin
- metamorphosis (normal growth and development)
- development of the nervous system
Goiter
The enlargement of the thyroid gland is called goiter (or struma). This can be accompanied by hypothyoidism or hyperthyroidism.
One possibility of the formation of goiter is the increased TSH level, which forces thyroid gland to develop hypertrophy and/or hyperplasia.
Or when the thyroid gland is not able to secrete hormones into the bloodstream and the pituitary gland produces high amounts of TSH as there is no inhibitory effect of the thyroid hormones.
The most well-known is the goiter caused by the lack of iodine. At the same time, substances, taken up from the environment and inhibiting functioning of the thyroid gland, cause the same hypothyroid goiter.
