The Thyroid Gland and Iodothyronines Flashcards
Describe the structure of the thyroid gland.
- Right, and left lobes + isthmus
- Occasional pyramidal lobe ( remnant of thyroglossal duct) above isthmus
- parathyroid glands embedded in thyroid
- Left recurrent laryngeal nerve runs close (vocal cord supply)
- 20g
- 4cm x 2.5cm x 2.5cm
- Right lobe is larger
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
What three main things does TSH stimulate in the follicular cell?
Stimulates IODIDE PUMPS to transport iodide from the blood into the cell at the basolateral membrane (facing the blood) Stimulates synthesis of THYROGLOBULIN Stimulates THYROID PEROXIDASE
Describe the formation of T3 and T4 in the follicular cell.
- In the presence of H2O2, thyroid peroxidase (TPO) can convert the iodide (which has been pumped into the colloid by the pendrin pumps) into a reactive iodine form. Iodide pumps are NIS (sodium iodide symporter) whilst pendrin pumps are I-/Cl- antiporters.
- TSH stimulates synthesis of thyroglobulin (diffuses into colloid) which is a long array of amino acids containing TYROSYL RESIDUES.
- Tyrosyl residues can be iodinated by the reactive iodine in ONE or TWO positions forming MONOIODOTYROSINE (MIT) and DIIODOTYROSINE (DIT) respectively.
- Continued stimulation of thyroid peroxidase will cause coupling reactions forming T3 and T4
At which positions are tyrosine iodinated?
3 and 5
Describe how iodothyronines 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) - Some T3 and T4 is transported by ALBUMIN (binds more loosely) - Prealbumin binds to a lot of T4 but little T3. - The BIOACTIVE component is the T3 and T4 that is UNBOUND
How do the latent periods and half-lives of T3 and T4 differ?
Latent Periods: T3 = 12 hours T4 = 72 hours Half Lives: T3 = 2 days T4 = 7-9 days
Describe the deiodination of T4.
T4 can be deiodinated in target tissues to produce T3 which is MORE ACTIVE T4 can be deiodinated in a different position to produce REVERSE T3 (which is INACTIVE)
What are the main actions of iodothyronines?
- Feotal Growth and devlopment
- Increase basal metabolism rate
- Protein, Lipid and Fat metabolism
- Potentiate action of catecholamines
- Effects on GI (diarrhoea) , CNS (agitation) and Reproductive System( irregular periods and infertility)
Iodothyronines are important in growth and development. What disease is caused by a lack of iodothyronines?
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 - Affects membrane transport pumps in the brain - Stimulates metabolic activity so has alot of effects on mitochondria
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 does iodine pumped into the colloid?
Pendrin pumps
How are T3 and T4 liberated?
- TSH stimulates lysosomes to move towards apical membrane
- T3/T4 uptaken into cell via endocytosis and they are now inside the lysozome
- Inside the lysozome, proteolysis cleaves T3 and T4 from the TG.
- T3 and T4 diffuses towards basolateral membrane and then diffuse into blood
Draw the Hypothalamo-adenohypophysial axis
