Lecture 6 - The thyroid glands and Iodothyronines Flashcards
Where is the thyroid located?
In the neck or trachea region
What are the key features of the thyroid gland?
Its formed of the right and left lobes - each with around 2 parathyroid lobes The middle triangle is composed of the lower part - isthmus and the upper part - pyramid Thyroid cells are arranged in follicles which are doughnut shaped - colloid in the centre ( thick, yellowish, proteinatious and gel-like substance) and follicular cells around it In between follicles are parafollicular cells which have endocrine functions
What is the endocrine function of paraventricular cells?
Ca2+ regulation
Describe the mechanism by which iodothyronines are synthesised
I- enters the follicular cells via the Na/I symporter and moves into I- into the colloid via a pendrian pump I- converted to I + Tg (thyroglobulin) via THYROID PEROXIDASE in presence of H2O2 This then forms either monoiodotyrosyl/diiodotyrosil MIT & DIT are the synthesised into T3 and T4 via coupling reaction using TPO and H2O2
How are T3 and T4 removed from the colloid?
TSH attaches to its receptor Stimulates endocytosis of T3 and T4 (colloid taken up and broken down by enzymes to form them) Then T3&4 filled vesicles are transported into the blood
What is the enzyme that causes iodination of I- into T3 and T4?
THYROID PEROXIDASE
Towards which cell membrane does the colloid face?
The apical membrane
What is the precursor molecule for iodothyronines?
Tyrosine
What are the steps in the synthesis of T3?
Tyrosine-> 3-monoiodotyrosine + 3,5-diiodotyrosine ->(coupling process) 3,5,3’-triiodothyronine (T3)
What are the steps in the synthesis of T4?
Tyrosine -> 2x 3,5-diiodotyrosine ->(coupling reaction) 3,5,3’,5’-tetraiodothyronine (T4/Thyroxine)
How are T3 and T4 transported in the blood?
Mostly bound to plasma proteins
Which plasma proteins is T3 transported with?
80% thyroid-binding/thyroxine globulin 15% albumin 2% pre-albumin 0.5% Bioactive component
What plasma proteins is T4 transported with?
70% thyroxine/thyroid-binding globulin 10% albumin 15% prealbumin 0.05% bioactive component
What is prealbumin now known as?
Transthyretin
Why do they need to be bound to proteins when transported in blood?
They are very easily taken up by cells, even if not target cells
Which of the plasma proteins that transport T3&4 is the most abundant and which is the least?
Thyroxine binding globulin most abundant Albumin least abundant (in this case)
What is a latent period?
Time taken for biological effect to occur after molecule (e.g. T3/4) in blood
What is the latent period for T3/4?
T3 around 12h T4 around 72h
What are the biological half lives of T3/4?
T3 around 2 days T4 around 7-9 days NB: longer than any other hormone
What is the main hormone produced by thyroid gland?
T4
What is the main use of T4?
It is deiodinated to T3 - acts as a source of T3 as T3 is MORE BIOACTIVE
Which is the more bioactive component between T3 and T4?
T3
What is another process that T4 can undergo?
It can be deiodinated in a different position leading to production of biologically INACTIVE molecule rT3
What does the thyroid do under starvation?
Synthesises more rT3 than T3/4 as the thyroid doesn’t need to be wasting energy, so it is ‘shut down’
What is the basal metabolic rate?
The level of metabolic activity happening in the body when inactive
What are the main actions of iodothyronines?
Increase basal metabolic rate (in most peripheral tissues -> calorigenesis) Increase protein, carbs and fat metabolism (important in normal growth and development)
What is the relationship between metabolism and weight in a hypERthyroid patient?
Weight decreases Increase CATAbolic metabolism
What is the relationship between metabolism and weight in a hypOthyroid patient?
Weight increases Increase ANAbolic metabolism
When do iodothyronines play an essential role and why?
During fetal growth and development Lack of IT results in CRETINISM - both mental and physical growth reduced (if untreated during 1st months)
How are IT levels tested in newborns?
Heel-prick test - measures IT levels in blood
What other actions do IT take part in?
Potentiate some of the actions of catecholamines (tachycardia, glycogenolysis, lipolysis) Interact with other endocrine systems Effects on CNS Increases Vit A synthesis
What is a sign of hypothyroidism?
Yellow skin - but NOT yellow sclera - due to carotene build up in blood
What is the mechanism of action of IT?
T4 and T3 enter the cell T4 -> into T3 (more biologically active) ***T3 and T4(less) increase protein synthesis, attaching to thyronine receptor (nucleus) increasing transcription*** T3 might stimulate membrane transport mechanisms and metabolic activity in mitochondrion
Summarise the thyroid production method
Hypothalamus -> TRH (Thyrotrophin) Adenohypophysis -> TSH (THYROTROPHIN - Thyroid stimulating hormone) Thyroid follicles -> T3 and T4
What are the inhibitory molecules in the negative feedback loop for IT?
SOMATOSTATIN Glucocorticoids Increase in T3 and T4 Increase in Thyrotrophin (TSH) Inorganic iodide (Wolff-Chaikoff effect)
What are the stimulatory molecules in the negative feedback loop for IT?
Oestrogens THYROTROPHIN RELEASING HORMONE
What cells in the adenohypophysis produce thyrotrophin?
Thyrotroph cells
How is iodothyronine production regulated in the negative feedback loop?
What is thyrostimulin?
2 unit glycoprotein
Where is thyrostimulin found?
Anterior pituitary (inc. heart, adipose, testis, ovary)
What does thyrostimulin bind to?
Thyrotrophin (TSH) receptor
