Endo 5 - Thyroid hormones Flashcards
Describe the structure of the thyroid gland.
It has two lobes joined by a narrowing called the ISTHMUS
It may have a remnant of the thyroglossal duct called the PYRAMID
Describe the cellular arrangement of the thyroid gland.
The cells are arranged in follicles
There are FOLLICULAR CELLS around the outside with a proteinaceous substance called COLLOID inside the follicles
There are parafollicular cells between follicles
Describe the hypothalamo- adenohypophysial-thyroid axis
The hypothalamus secretes TRH (thyrotrophin releasing hormone).
TRH signals to the anterior pituitary to release thyrotrophin (also known as TSH).
TSH stimulates the production of the iodothyronines T3 and T4.
T3 and T4 inhibit the secretion of TSH and TRH by negative feedback.
Wolff-Chaikoff Effect: Ingestion of a large amount of iodine reduces the production of T3/T4.
Describe thyroid hormone synthesis
- TSH binds to the TSH receptor on the basolateral membrane of the follicular cell.
- Iodide Trapping: Iodide is actively co-transported with sodium (secondary active transport) by the Sodium-Iodide Symporter (NIS). [Sodium is actively exchanged with potassium and is pumped out of the cell by the Na/K ATPase.]
- Iodide ions diffuse to the apical memrane of the cell, and is pumped into the colloid using the Pendrin Pump. This works as an Iodide/chloride exchanger/antiporter. A genetic disease of the Pendrin pump is called Pendred Syndrome.
- TSH stimulates TG synthesis in the cell. It diffuses to the colloid, where it is present in large amounts.
- In the colloid, TPO (thyroid peroxidase) oxidises I- to I* in the presence of H2O2.
- I* is then quickly attatched to a tyrosine on a molecule of TG. This reaction is also catalysed using TPO in the presence of H2O2.
- If one I* is added to the TG-tyrosine, it is called a mono-iodotyrosyl (MIT).
- If two I* are added to the TG-tyrosien, it is called a di-iodotyrosyl (DIT).
- Coupling occurs: TPO and H2O2 combine a DIT from one TG to either an MIT or another DIT on another TG: DIT+MIT gives a T3 hormone; DIT+ DIT gives a T4 hormone. T3 and T4 are still bound to TG at this stage.
- A lysozome moves towards the apical membrane.
- T3/T4-TG are taken up into the cell via endocytosis, they are now inside the lysozome.
- Inside the lysozome, proteolysis cleaves T3 and T4 from the TG.
- The T3/T4 diffuse towards the basolateral membran and then diffuse into the blood. They are secreted to have an action all around the body.
What three main things does TSH stimulate in the follicular cell?
Stimulates IODIDE CHANNELS to transport iodide from the blood into the cell at the basolateral membrane (facing the blood)
Stimulates synthesis of THYROGLOBULIN
Stimulates THYROID PEROXIDASE
At which positions are tyrosine iodinated?
3 and 5
Describe how T3 and T4 are transported in the blood
To prevent uptake by non-target tissues, T3 and T4 are mainly transported by PLASMA PROTEINS
The majority of T3 and T4 are transported by THYROXINE BINDING GLOBULIN (TBG) 70-80%
Some T3 and T4 is transported by ALBUMIN (binds more loosely) 10-15%
Prealbumin aka transthyretin
The BIOACTIVE component is the T3 and T4 that is UNBOUND
Only 0.05% T4 unbound and 0.5% T3
How do the latent periods and half-lives of T3 (triiodothyronine) and T4 (thyroxine) differ?
Latent Periods: T3 = 12 hours T4 = 72 hours Half Lives: T3 = 2 days T4 = 7-9 days
Describe the deiodination of T4 (thyroxine).
T4 can be deiodinated to produce T3 which is MORE ACTIVE. Enzyme is deiodinases
T4 can be deiodinated in a different position to produce REVERSE T3 (which is INACTIVE)
So T3 is the major thyroid hormone
T4 is the major secretory product - it is predominant - 80%
Describe the mechanism of action of thyroid hormones
The Thyronine Receptor (TR) is intracellular.
T4 (+ some T3) enter the cell. T4 is converted via deiodination to T3.
T3 binds to the TR in the nucleus.
This acts in the nucleus, where it affects transcription and protein synthesis.
However, it is also thought that T3 acts via different ways as well. T3 has many rapid effects –these cannot be explained by genomic phenomena (i.e. since it takes a long time to alter transcription and translation, T3 must act via different mechanisms as well if it is tp produce these rapid effects).
The other mechanisms include: metabolic activities in the mitochondria and altering membrane transport mechanisms.
What are the main actions of iodothyronines?
Increase Basal metabolic rate (BMR).
Increase Protein, carbohydrate & fat metabolism
Potentiate actions of catecholamines [Adrenalne and noradrenaline] (e.g. tachycardia, lipolysis)
Effects on the GI, CNS, Reproductive system
Fetal growth & development. Cretinism: Physical and mental developmental problems due to congenital hypothyroidism. There is a heel-prick test for newborns, testing for cretinism.
Describe the action of iodothyronines on target cells
Thyroid hormones are NOT steroid hormones but they are LIPID SOLUBLE
They bind to intracellular receptors and have a genomic effect
State two hormones that increase iodothyronine production.
Thyroid Stimulating Hormone (adenohypophysis)
Oestrogens
State some factors that decrease iodothyronine production.
T3/T4 negative feedback (direct and indirect)
Somatostatin
Glucocorticoids
Ingestion of large amounts of inorganic iodide
Thyrotrophin (autonegative feedback loop)
How much does the thyroid weigh?
20g
