PH1124 - thyroid hormones Flashcards
how and when does the thyroid gland develop? (3)
- appears very early in life
- develops about four weeks after conception as an epithelial invagination of the tongue
what is the anatomy of the thyroid gland? (4)
- composed of 2 large lobes either side of the trachea below the larynx and joined by the isthmus
- there is a rich blood supply from thyroid arteries
- innervated by the autonomic nervous system
- pyramidal lobe is often present
- butterfly shape
what is the cellular structure of
the thyroid gland? (3)
- its cells are arranged in follicles
- there are millions of follicles in a thyroid gland
- follicles are spherical bodies composed of epithelial cells surrounding a colloidal storage protein (thyroglobulin)
what does the height of epithelial cells depend on in the thyroid gland? (2)
- inactive; epithelial cells are flattened with a large colloidal mass
- active; cells are columnar in shape with a small colloidal lumen
what are the parafollicular C cells?
- large epithelial cells that lie between the follicles and produce calcitonin
what are the main hormones produced by the thyroid gland? (2)
- T3
- T4
how are thyroid hormones made?
- dietary iodide is taken up by an iodide pump from the blood
- at the apical surface I- is oxidised by hydrogen peroxide from thyroid peroxidase to I2
- I2 is immediately incorporated into tyrosyl residue covalently bound to thyroglobulin TG at apical border to form MIT and DIT
- MIT and DIT are coupled by thyroid peroxidase to form T3 and T4
how are thyroid hormones secreted?
- TSH causes endocytosis and proteolysis by lysosomes of TG-hormone complex
- this is where thyroids hormones are stored in the colloid
what simulates the uptake of iodide by the thyroid? (3)
- TSH (thyroid stimulating hormone)
- iodine deficiency
- TSH receptor antibodies
what are the anions that inhibit the iodine pump? (4)
- I-
- perchlorate (ClO4-)
- thiocyanate (SCN-)
- pertechnetate (TcO4-)
how are the thyroid hormones transported? (2)
- transported in the plasma bound to proteins where T3 is less avidly bound than T4
- only free hormone not bound is biologically active
what are the proteins that thyroid hormones bind to in plasma? (3)
- thyroid binding globulin
- transthyretin
- albumin
which thyroid hormone is more potent?
- T3 is approx 10 times more potent than T4
how are thyroid hormones metabolised? (2)
- T4 is de-iodinated to T3 in the periphery (liver and kidney)
- T3 and T4 are conjugated to glucuronide or sulphate in the liver and excreted in the bile
how is iodine excreted?
- excreted in the urine or re-circulated to the thyroid
what is TRH?
- thyrotropin releasing hormone
how is the release of thyroid hormones regulated?
- a stimulus causes the hypothalalmus to release TRH which causes the anterior pituitary to release TSH
- this causes the thyroid glad to produce T3 and T4
- this directly stops the productions of TSH from the anterior pituitary therefore its a negative feed back loop
how do somatostatin and dopamine effect the production of T3 and T4?
- they cause the release of TSH from the anterior pituitary to be inhibited
- less T3 and T4 is secreted from the thyroid gland
what is the role of TRH? (2)
- stimulates the release of thyrotrophin or thyroid stimulating hormone (TSH) from the anterior pituitary
- releases prolactin
what is TSH?
- thyroid stimulating hormone
what does TSH do to the thyroid?
- acts on specific receptors on basal membrane
- increases synthesis of iodine pumps, thyroglobin and thyroid hormones
what is the release of TSH inhibited by? (6)
- thyroid hormones
- cortisol
- growth hormone
- oestrogens
- dopamine
- somatostatin
what is the mechanism of action for thyroid hormones at the nuclear level? (5)
- T3 and T4 enter the cell by passive diffusion or active uptake
- T4 is then de-iodinated to T3
- T3 is actively transported into the nucleus and binds to cytosolic thyroid hormone binding protein (CTBP)
- this ensures T3 binds to thyroid receptors in the nucleus already bound to regulatory thyroid hormone response elements TREs
- thyroid hormone receptor auxiliary protein (TRAP) is then necessary to stabilise TR binding to DNA to either transcribe or inhibits genes
what is the mechanism of action for thyroid hormones at the cellular level? (3)
- T3 binds to membrane-associated receptors to activate Na+/K+ ATPase pump
- this causes an increased uptake of glucose and amino acids
- T3 also directly activates mitochondria to increase energy production
how do thyroid hormones control basal metabolic rate?
- via calorienesis
what is calorigenesis?
- increase O2 consumption in all tissues (except brain, spleen, testes and anterior pituitary) causing increased heat production
- iimportant for thermoregulation
- does this by synthesizing new ATPase pumps in cell membrane but also directly activates mitochondria
what does calorigenesis block?
- blockers of Na+/K+ ATPase pumps such as cardiac glycosides (dogoxin) inhibit actions of thyroid hormones
what are the physiological actions of the thyroid hormones?
- calorigenesis
- carbohydrate, protein and fat metabolism
- maturation of central nervous system
- skeletal growth and maturation
