Thyroid Hormone Physiology Flashcards
What is the largest endocrine gland?
Thyroid
What is the main function of the thyroid?
Regulate basal metabolic rate
What dietary substance does the thyroid need to function?
Iodine
What is dietary iodine (I2) absorbed as?
Iodide
The thyroid is located below which structure? Which cartilage is it located at either side of?
Below the larynx
Either side of thyroid cartilage (cricoid cartilage)
Which two muscles is the thyroid covered by?
Strap muscles from the neck and overlapped by sternocleidomastoid
What fascia is the thyroid enclosed by?
Pretracheal fascia - attaches thyroid to the larynx
Where does the thyroid gland develop from?
Floor of the pharynx, near the root of the tongue.
It descends into he neck as a down growth.
What colloid substance are thyroid follicles rich in?
Thyroglobulin
What type of protein is thyroglobulin?
Large tyrosine rich dimeric glycoprotein
What hormones does the thyroid gland secrete?
T4 - Thyroxine (majority)
T2 - Triiodothyronine
T4 + T3 originate from which hormone?
Tyrosine
They have added iodine (T4 = 4, T3 = 3)
Which thyroid hormone has a longer half life?
T4
What do thyroid C cells produce and what is it involved in?
Calcitonin
Involved in calcium homeostasis
Which hormone is a precursor of T3?
T4.
Can be converted to active T3 via removal of one iodine.
T4 is converted to T3 primarily in which extra-thyroidal tissues?
Liver and Kidneys
How is iodine removed from T4 to convert this into T3?
Via Iodothyronine deiodinase
What are the three types of deiodinases?
D1 - liver, kidney, thyroid
D2 - Muscle, brain, pituitary, skin and placenta
D3
Which deiodinase creates active T3 and how?
D1 + D2
Via outer ring deiodination
Which deiodinase creates inactive T3 and how?
D3
Via inner ring deiodination
How is thyroglobulin synthesised?
Thyroglobulin and thyroid peroxidase are synthesised in the RER –> Then transported to Golgi –> Packaged in vacuoles –> Thyroglobulin exocytosis into colloid space through microvilli. Thyroid peroxidase sits on apical membrane.
Iodide enters cell –> transported to apical border via Pendrin where there are microvilli –> Iodide converted to iodine + iodine binds to thyroglobulin, both via thyroid peroxidase.
This creates Iodinated thyroglobulin that is stored in colloid.
How is thyroglobulin broken down?
Colloid droplets from colloid space go though endocytosis into apical cell membrane.
Lysosome fuses with droplet + enzyme breaks thyroglobulin down into T3 + T4
What type of cells are thyroid cells?
Cuboidal epithelial cells
Which protein assists Iodide across the cell into the colloid space?
Pendrin
How does iodide enter the basolateral membrane of the thyroid cell?
Via Sodium/Iodide symporter
Thyroid peroxidase binds tyrosine and iodine to create which molecules in the colloid space?
X1 Iodine + Tyrosine = MIT (Monoiodotyrosine)
X2 Iodine + Tyrosine = DIT (Diiodotyrosine)
MIT + DIT are coupled together via thyroxine peroxidase and transported back into the apical membrane of the cell via which process?
Endocytosis
In the Thyroid follicular cell, MIT + DIT, and DIT + DIT are bonded to create which hormones?
DIT + DIT = T4
MIT + DIT = T3
The Sodium/Iodide Symporter is reliant on the sodium gradient created by which pump?
Na+/K+ ATPase
The Sodium/Iodide Symporter transports 1 iodide ion against how many sodium ions?
2
What regulates thyroid hormone secretion?
Hypothalamus Pituitary Thyroid Axis
How does the HPT Axis work?
Hypothalamus releases Thyrotropin Releasing Hormone (TRH) –> Stimulates anterior pituitary to release Thyroid Stimulating Hormone (TSH) –> Production of T3 + T4 in thyroid –> Negative feedback loop to hypothalamus and anterior pituitary to inhibit TRH + TSH secretion.
Thyrotropin releasing hormone (TRH) is transported to the pituitary via which system?
Hypothalamic - Hypophyseal portal system
Which cells in the anterior pituitary gland produces TSH?
Thyrotrope cells
TSH receptor binding activities which enzymes?
AC –> cAMP
PLC
How does cold exposure affect thyroid hormone stimulation?
Hypothalamus mechanism that controls body temperature gets excited –> increases production and secretion of TRH –> reduces metabolic rate
How does fasting affect thyroid hormone stimulation?
Fasting reduces leptin levels –> reduces expression/secretion of TRH, TSH + thyroid hormones –> reduces metabolic rate
How does emotion affect thyroid hormone stimulation?
Emotional reactions stimulate the SS –> decreased TSH secretion.
What are T4 + T3 bound to in the blood?
Plasma proteins.
E.g. Thyroxine binding globulin (TBG), Thyroxine binding prealbumin or transthyretin (TTR) + Albumin (All liver synthesised)
How quickly are T4 + T3 released into tissues from blood?
Half of blood T4 released every 6 days
Half of blood T3 released every day as there is lower affinity to plasma proteins.
How to T3 + T3 enter cells?
via active membrane transport.
MCT8 transporter protein.
Which hormone binds to Thyroid hormone receptors?
T3 - high affinity binding.
Thyroid hormone receptors need to bind to which other receptors to form heterodimers?
Retinoid X Receptors (RXR)
Once T3 binds to Thyroid Hormone Receptors + Thyroid Hormone Receptors bind to Retinoid X Receptors, what does this allow Thyroid Hormone Receptors to bind to?
Thyroid Hormone Response elements/Hormone response elements (HRE).
These are short DNA sequences that regulate gene expression.
What cellular mechanisms are affected in response to thyroid hormone activity?
Which body functions are affected in response to thyroid hormone activity?
