59) The Thyroid gland Flashcards
1
Q
What is the function of the thyroid hormone?
A
- Developmental: It is essential for normal growth and development
- Metabolic: It is essential for normal metabolism in the body.
2
Q
How does TH increase metabolic rate?
A
- Increasing size and number of mitochondria, enzymes and Na/K ATPase activity
- Positive isotropic and chronotropic effects on the heart
- Synerzies with sympathetic nervous system
3
Q
What does the TH do in energy metabolism?
A
- It partially antagonizes insulin signalling
- Gluconeogenesis and lipolysis
4
Q
Describe the structure of the thyroid
A
- The thyroid is a bi-lobed gland around the trachea that produces thyroid hormones
- It contains a left lobe, right lobe and an medial pyramidal lobe
- It contains thyroid follicles on its surface where the thyroid gland secreting cells are located
- It has a very rich blood supply and is supplied by two arteries: Superior thyroid artery (coming from the carotid artery) and the inferior thyroid artery (coming from the subclavian artery)
- Follicular cells surround spherical structures filled with colloid (which consists of mainly of a protein called thyroglobulin)
- These follicular cells synthesise and secrete thyroid hormones
5
Q
What are the different thyroid hormones?
A
- Thyroxine (T4): Has 4 iodine atoms attached. It is the major form that is released into circulation and is less active. It is considered to be a prohormone
- Triiodothyronine (T3): Has 3 iodine atoms attached. It is the active form and is converted from T4 to T3 in target cells
6
Q
How are thyroid hormones formed?
A
- They are formed when tyrosine residues are condensed together and iodinated in specific places
- If iodine is found in the wrong place of a thyroid hormone it is inactive (e.g. reverse T3 has 3 iodine atoms in the wrong places)
7
Q
Describe the mechanism of TH synthesis and release
A
- Many of the steps involved are stimulated by TSH (Thyrotropin stimulating hormone) secreted by the anterior pituitary gland
- First we have the uptake of I- from extracellular fluid via secondary active transport coupled to Na2+ electrochemical gradient (the gradient is maintained by the Na+/K+ ATPase)
- I- is then passed out of the cell into the colloid where it is oxidised to I2 and is then covalently bound to tyrosine residues in the thyroglobulin (that is already located in the colloid)
- This requires the enzyme Thyroid peroxidase and hydrogen peroxide (H202) and forms a tyrosine residue with covalent iodine binding that is either monoiodotyrosine or diiodotyrosine
- They are then endocytosed into the follicular cell where the thyroglobulin is cleaved to release T4 or T3
- The hormone is then exported into circulation via transporters in the membrane
8
Q
How does thyroid hormones travel in circulation?
A
- Firstly most of the thyroid hormones released are T4 with small amount being T3
- Most of the released thyroid hormones travels bound to plasma proteins
- It is mainly bound to thyroid-binding globulin however a small fraction is also bound to transthyretin and albumin
- The rest of the thyroid hormones (those not bound to plasma proteins) are free in the plasma
9
Q
What are thyroid hormone receptors?
A
- TH receptors (TRs) belong to the nuclear receptor superfamily
- They function as ligand-activated transcription factors where binding of the receptor leads to induced increased/decreased expression of various genes
- They have a higher affinity for T3
- In order to be activated they require dimerization with another TR or Retinoid X Receptor (RXR)
- The TRs are encoded for by two genes: TR alpha and TR beta
- Each gene comes in two isoforms due to alternative splicing however only 3 of the 4 isoforms are functional (TR alpha 2 is non functional)
10
Q
Describe the structure of a nuclear receptor.
A
- There are three main domains
- At the N-terminal end there is a domain where different co-regulatory/transcription factors bind
- Then there is a DNA binding domain in the middle which provides specificity and is the part that binds to the promoter regions of the DNA called Hormone response elements (in the case of thyroid hormones it is a Thyroid Response element/TRE)
- Finally there is the hormone recognition element which is responsible for dimerization and binding with the hormone
11
Q
What happens when a thyroid hormone binds to its receptor?
A
- Upon binding there is a shift in the pattern of various coregulatory transcription factors which activates transcription of target genes
12
Q
How are TH metabolically regulated at target tissue?
A
- Relative levels of T3 to T4 and other inactive forms of the hormone can be controlled in target tissue
- This is done via three enzymes called iodothyronine selenodeiodinases which are D1-3 (seleno refers to trace element selenium which shows why selenium is important in the diet)
- These enzymes can interconvert between T4 and T3 and they can also these hormones into completely inactive forms
- D2 increases T3 levels while D3 decreases T3 levels
- This changes the amount of T3 available for binding to its receptor
13
Q
How do TH enter target cells?
A
- There are membrane transporters for thyroid hormones which are required for the hormone to enter target cells
- Mutations in the genes for these transporters leads to disorders
14
Q
How is the secretion of TH regulated?
A
- The release of thyrotropin-releasing hormone (TRH) by hypothalamic neurosecretory cells into the median eminence stimulates the release thyroid stimulating hormone (TSH)
- Here it diffuses into portal capillaries which travels to the anterior pituitary lobe triggering the release of TSH
- TSH then drains into the circulation where it stimulates thyroid follicular cells to synthesise and secrete TH
- This system is under negative feedback as T4 and T3 can inhibit the release of TSH (from the hypothalamus) and/or TSH (from the anterior pituitary lobe).
- They do this when they travel to the glands (hypothalamus and anterior pituitary) through the capillaries and bind to them
15
Q
How does levels of TH affect pituitary and hypothalamus activity?
A
- If levels of T4 and T3 rise then activity of the glands decrease
- If levels of T4 and T3 fall then activity of the glands increases
