Thyroid gland Flashcards
What is the structure of the thyroid gland?
Two lobes, right and left
Joined together in the middle by the isthmus
What is the pyramidal lobe?
Extends upwards from the middle of the thyroid
How many people have the pyramidal lobe?
Only a few
What does the thyroid gland lie in front of?
The larynx and the trachea
What does the thyroid gland lie below?
Thyroid and cricoid and cartilage
What does the thyroid gland lie above?
Suprasternal notch
What does the isthmus lie in front of?
2nd - 3rd rings of cartilage of trachea
What is the pretracheal fascia?
Fascia that joins the thyroid gland
to the trachea and larynx
Why does the thyroid gland moves upward on swallowing?
Because the larynx moves up when swallowing
pulls on pretracheal fascia
pulls up thyroid gland
How many parathyroid glands are there?
Four
Where are the parathyroid glands located?
Behind the thyroid gland
What are thyroid follicles made up of?
Follicular cells
arranged in spheres
Extracellular colloid within the spheres
Parafollicular cells located between follicular cells
What do follicular cells do?
Produce thyroglobulin, thyroid hormones
What does the colloid store?
Thyroglobulin
How do the follicular cells transport thyroglobulin into the colloid?
Exocytosis on their apical domain
What do parafollicular cells produce?
Calcitonin
What does calcitonin have a role in?
Calcium homeostasis
What is the histology of the parathyroid gland?
Principle/chief cells
What do principle/chief cells do?
Produce parathyroid hormone
What happens to iodine in the GI tract?
Reduced to iodide I-
What happens to iodide in the GI tract?
Taken up by epithelial cells in the small intestine
Absorbed into blood
Where is iodine found in the body?
Mostly in the thyroid gland
Which molecules of the body contain iodine?
monoiodotyrosine, MIT
diiodotyrosine, DIT
triiodothyronine, T3
thyroxine, T4
What is MIT made up of?
Tyrosine
One iodine attached to its aromatic ring
What is DIT made up of?
Tyrosine
Two iodines attached to its aromatic ring
What is T3 made up of?
MIT and DIT joined together
Two tyrosines, three iodines
What is T4 made up of?
Two DIT molecules joined together
Two tyrosines, four iodines
How is iodide taken up by follicular cells?
By the sodium iodide trap
Where is the sodium iodide trap located on follicular cells?
Basolateral domain
What happens to iodide in the follicular cells? What type of reaction is this?
I- —–> I2
oxidation
What enzyme catalyses the reaction
I- —–> I
in the follicular cells?
Thyroid peroxidase
What additional molecule is required to be present for the oxidation of iodine?
Hydrogen peroxide H2O2
What happens to iodine in the follicular cells?
It diffuses into the colloid
What happens to iodine and thyroglobulin in the colloid?
Thyroglobulin tyrosine residues are iodinated
forming MIT and DIT on thyroglobulin
What enzyme catalyses the iodination of thyroglobulin in colloid?
Thyroid peroxidase
Thyroid peroxidase catalyses oxidation, iodination and….
Coupling
What happens in the coupling reaction?
MIT and DIT are joined together
to form T3 and T4
on thyroglobulin
How do follicular cells take up thyroglobulin from the colloid?
Pinocytosis in the apical domain
What is the pinocytosed thyroglobulin contained in inside the follicular cell?
Vesicle
What happens to the vesicle containing thyroglobulin?
Lysosome fuses with it
What happens to the thyroglobulin inside the phagolysosome?
It is digested by proteases
releasing T3 and T4
What happens to the isolated T3 and T4 in the follicular cells?
Diffuse across the basolateral domain of the follicular cells
enter the blood
Which is secreted into the blood more - T3 or T4?
T4
Why do T3 and T4 not dissolve in the blood?
Are hydrophobic
Insoluble in water
How are T3 and T4 carried in the blood?
By binding to thyroxine-binding globulin!
Which is more biologically active - T3 or T4?
T3
Where is T4 converted into T3?
Liver
Kidneys
Where are thyroid hormone receptors located?
Inside the cell
Inside the nucleus - are nuclear receptors
How does thyroid hormone enter cells?
Through thyroid hormone transporters
How does thyroid hormone enter the nucleus?
Through the nuclear pores
Where is the thyroid hormone receptor inside the nucleus?
Is pre-bound to specific DNA sequences
What are the specific DNA sequences that the thyroid hormone receptor is pre-bound to? What are they called?
Promoter region of thyroid regulated gene
Thyroid hormone response elements
How does the thyroid hormone receptor affect the thyroid regulated gene?
It represses transcription of the gene
When thyroid hormone binds its receptor, what happens to the receptor?
Undergoes conformational change
Becomes transcriptional activator
How does the changed thyroid hormone receptor affect the thyroid regulated gene?
Relieves its repression
Results in the gene being transcribed, translated, protein produced
What are some examples of proteins produced by thyroid hormone activated genes?
Ca2+ ATPase
Na+ K+ ATPase
Cytochrome oxidase
PEPCK
How do thyroid hormones affect cells?
Affect cell differentiation
cell development
both linked to metabolism
What are the general effects of thyroid hormone?
Increase in BMR, heat production
Stimulation of metabolic pathways
Sympathomimetic effects
How does thyroid hormone increase BMR, heat production?
Increasing number AND size of mitochondria
Stimulating synthesis of enzymes in electron transport chain
Which tissues do not undergo and increase in BMR, heat production by thyroid hormone?
Brain
Spleen
Testes - for sperm production
What general type of metabolic pathway do thyroid hormones tend to stimulate?
Catabolic
How does thyroid hormone affect carbohydrate metabolism?
Increase in GLUT4 transporters, insulin dependent entry of glucose
Gluconeogenesis
Glycogenolysis
How does thyroid hormone affect lipid metabolism?
Stimulates lipolysis
B-oxidation of fatty acids
How do thyroid hormones have sympathomimetic effects?
Increase catecholamine receptors on cells
larger response to catecholamines
Which tissues are specifically affected by thyroid hormone?
CVS
Nervous sustem
How is the CVS affected by thyroid hormones?
Increased response to catecholamines gives…
-increased heart rate
-increased force of contraction
=increased cardiac output
-peripheral vasodilation
to carry extra heat to body surface
How is the nervous system affected by thyroid hormones?
Required for development and function of neruones
e.g. their myelination
How is the release of thyroid hormone regulated?
HPT axis
Outline the HPT axis
Hypothalamus releases….
Thyrotropin releasing hormone (TRH) …. which stimulates….
Anterior pituitary …which releases….
Thyroid stimulating hormone …which stimulates…
Thyroid gland …which releases…
T3 and T4 …which inhibit the anterior pituitary, inhibit the hypothalamus - long loop
TSH inhibits the hypothalamus via the short loop
What type of hormone is TSH?
Glycoprotein hormone
What is the structure of TSH?
Two subunits
a and B
joined by covalent bonds
What other hormones is the a subunit present in?
FSH
LH
What does the B subunit confer?
Specifity
What type of receptor is the TSH receptor?
GPCR
What G proteins is the TSH GPCR coupled to? What are the final outcomes of these G proteins?
Gas - gives PKA
Gaq - gives PKC, Ca2+ increase
What is the outcome of TSH binding to its receptor?
Stimulate thyroid hormone synthesis and release
How exactly does TSH binding to its receptor stimulate thyroid hormone synthesis and release?
Iodide uptake Iodide oxidation to iodine Thyroglobulin synthesis Thyroglobulin iodination Thyroglobulin pinocytosis Thyroglobulin proteolysis
Why might free T3 and T4 levels show variation that’s not due to disease?
Factors to do with method
Changes in albumin levels - also carries thyroid hormones in blood, but to lesser extent
Dilution effects
Why might free TSH levels show variation that’s not due to disease?
Variation depending on time of day
Pulsatile secretion
Medications
What is the first endocrine gland to develop in the embryo?
Thyroid gland
When does the thyroid gland begin to develop?
3-4 weeks
How does the thyroid gland first appear?
Epithelial proliferation
Where does the thyroid gland first appear?
Floor of pharynx
Base of tongue
What direction does the developing thyroid gland move in?
Descends downwards
What does the developing thyroid gland descend as?
Thyroid diverticulum
What does the descending thyroid gland move through?
The thyroglossal duct
How does the developing thyroid gland move in relation to the hyoid bone?
In front of the hyoid bone
Then behind the hyoid bone
What happens to the thyroglossal duct?
It degenerates
What is lingual thyroid?
Remnant of thyroid tissue on tongue
What is a thyroglossal duct cyst?
Remnant of thyroglossal duct
Shows up as swelling in anterior neck
How does a thyroglossal duct cyst move when the tongue us protruded? Why?
Moves inwards and upwards
because is connected to tongue
How many cells in the body does thyroid hormone affect?
All of them!
Where is a thyroglossal duct cyst located?
Near hyoid bone
Always in the midline