Thyroid Hormones Flashcards
Name the hormones produced by the thyroid gland
thyroxine - T4, inactive
tri-iodothyronine - T3, active
calcitonin
What are the six steps in thyroid hormone synthesis?
- thyroglobulin synthesis
- uptake and concentration of iodide
- oxidation of iodide to iodine
- iodination of thyroglobulin
- coupling of two iodinated tyrosine molecules to form T3 or T4
- Secretion
How does the thyroid gland trap iodide ions?
Thyriod follicles actively accumulate iodide from the blood and secrete it into colloid.
Iodide enters the cell by a Na+/Iodide symporter located on the basolateral surface of the follicle cell.
A Na+/K+ATPase pumps Na+ out of the follicle cell into the blood which maintains a Na+ gradient.
Describe how thyroid hormone is synthesized
- Iodide is transported into the cell and oxidised to iodine
- Thyroglobulin chains are synthesised from tyrosine
- Iodine binds to tyrosine residues to produce MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
- MIT and DIT are conjugated by coupling reactions to produce T3 and T4. T4 is the major product of the reaction.
- The products remean in a peptide linkage attached to thyroglobulin and are stored in the colloid of the follicle
Explain how thyroid hormones are released
When the thyroid gland is stimulated to secreted thyroid hormone, the thyroglobulin complex is taken up into follicle cells by endocytosis.
The endocytic vesicle fuses with lysozomes and hydrolyse the complex to release T3, T4, DIT and MIT into the cytosol.
T3 and T4 are released from the follicular cell and enter the capillary circulation where they bind to thyroid binding globulin to be transported.
The DIT and MIT are deiodinated and the iodine is recycled. to make more thyroid hormone
How are levels of T3 in peripheral tissues regulated?
Levels of T3 are regulated in peripheral tissue by deiodinases.
Type 1 - present on the cell surface of most cells increase T3 levels by converting T4 to T3
Type 2 - increases intracellular T3 in the CNS and pituitary gland by converting T4 to T3
Type 3 - present in the placenta and CNS. Removes iodine from T4 to make reverse T3 which is inactive.
Name two signs and two symptoms of hyperthyroidism
Signs: Goitre, nervous irritability
Symptoms: weight and muscle loss, increased appetite, heat tolerance, sweating
When levels of T3/T4 are high enough to cause symptoms it is called thyotoxicosis
Name two signs and two symptoms of hypothyroidism
Signs: goitre, alopecia, slow responses
Symptoms: lethargy, weight gain
When levels of T3/T4 are low enough to cause symptoms it is called myxoedema
What is TSH?
Thyroid stimulating hormone- glyoprotein hormone released from the anterior pituitary gland
How do both low and high T4 induce a goitre?
Low:
In patients with iodine deficiency, a lack of iodine means that thyroid gland canot make sufficient quantities of thyroid hormones. Low levels of T4 means that there is a lack of product inhibition back to the anterior pituitary gland. Therefore more TSH is released in response to the low levels of circulating thyroid hormone. This increases the size of the thyroid gland, producing a goitre
High:
In patients with Grave’s disease an autoantibody is produced against the TSH receptor on follicular cells of the thyroid gland and mimics the effects of TSH. This increases the production of thyroid hormones. High levels of T4 inhibits the anterior pituitary and less TSH is released however the thyroid gland is still stimulated to produce more hormone. This inceases the growth of the thyroid gland, resulting in a goitre
Describe the physiologic actions of thyroid hormones
CNS development: stimulates myelinogenesis, synapse formation and neuronal outgrowth
Body growth: promotes calcification of bone, stimulates synthesis of structural and enzymatic proteins
Metabolism: Affects basal metabolic rate, thermogenesis cellular respiration, has anabolic and catabolic effects
Describe the mechanism of action of thyroid hormone
The thyroid hormone receptors are located in the nuclei of target cells bound to thyroid hormone response elements in the DNA.
Target cells take up T3 and T4 from the blood in an active carrier mediated process.Inside the cell, T4 is deiodinated to T3 which is able to enter the nucleus and bind to the thyroid receptor.
The activated thyroid receptor binds to the retinoic acid receptor (RXR) to form a complex which binds to the thyroid response element. This displaces the repressors of transcription and recruits coactivators and RNApolII, initiating transcription of the target gene.
How does the thyroid hormone receptor enable the thyroid hormone to have different effects on tissues?
The genes for the thyroid hormone receptor are found on two different genes and encode several different proteins. Splice variants of the receptors means that multiple isoforms can exist which increases the variation of specificities and activty.
The thyroid hormone receptors are expressed in a tissue specific manner and therefore thyroid hormones will have different effects on different tissues depending on the receptor that is present
Receptors can bind to the DNA as monomers, heterodimers or homodimers, which can also mean that the response varies.
Name two dietary sources of iodine
Seafood
Sea salt
Fruit and vegetables
Describe the structure of the thyroid gland
Made up of two lobes attached to each side of the trachea connected by an isthmus which lies just below the cricoid cartilage.
The lobes of the thyroid gland consist of aggregated follicles lined by epithelial cells. The lumen of each follicle contains colloid which is mostly made up of thyroglobulin. Parafollicular cells in wall of the follicle make calcitonin.
