endocrinology: thyroid Flashcards
what can reduce thyroid hormone production
iodine deficiency
describe the thyroid hormone axis
TRH released from hypothalamus stimulates TSH in anterior pituitary which stimulates thyroid follicle where thyroid hormones (T3/T4) are made and stored, T3/T4 provide negative feedback for both TSH and TRH.
T4 is a prohormone, an iodine is cleaved off to make T3 which is biologically active
describe the thyroid follicle
in the thyroid follicle there are follicular epithelial cells which have TSH receptors, inside these cells is an area called the colloid space
between thyroid follicles are c cells which produce calcitonin
stimulation of TSHRs by TSH causes synthesis, regulation and release of thyroid hormones.
how is iodine transported into thyroid follicle
There are sodium iodine transporters on the thyroid follicular cells which transport both sodium and iodine into the cell, the iodine is then transported from the cell to the colloid space via a transporter called pendrin.
what is precursor for thyroid hormone other than iodine
thyroglobulin is another precursor for thyroid hormones, protein made in the ER of the follicular cells, also exported into colloid space via exocytosis, thyroglobulin is a long chain of tyrosine molecules
In the colloid space the iodine is added to thyroglobulin using thyroid perxoidase enzyme (TPO), this creates T3 and T4 which are bound to the thyroglobulin, which are then transported back into follicular cell via endocytosis, where it is broken down into T4 and T3 using lysosomes.
how are thyroid hormones transported to/in blood, how is it stored
T3 and T4 are transported into the blood via transporter MCT8.
thyroid hormones are very hydrophobic, more than 99% of circulating T3 and T4 in blood is bound to carrier proteins.
main carrier of thyroid hormones is thyroxine binding globulin, a glycoprotein synthesized in the liver. Other important carriers are thyroxine binding prealbumin and albumin.
carrier proteins allow maintenance of a stable pool of thyroid hormones from which the active free hormones are released for uptake by target cells.
T3 and T4 last for 3 months in colloid matrix since they are stored attached to thyroglobulin.
how is T4 converted at site of action
conversion of T4 to T3 occurs in cytosol after being transported into the cell
describe perfusion of thyroid gland
high blood flow through thyroid gland, 4-6ml/min/g of thyroid tissue (double flow through kidney). high rate is important for delivery of iodide and TSH and secretion of T3 and T4
where is iodine found in the body
only in the thyroid
what are major steps of thyroid hormone synthesis, how does TSH effect this
production and accumulation of raw materials (iodine and thyroglobulin transport)
synthesis of the hormones on a scaffold of precursors (iodination of tyrosine molecules on thyroglobulin)
release of the free hormones from scaffold (lysozyme digestion) and secretion into blood (through MCT8 with carrier proteins)
each of these processes is stimulated by TSH from anterior pituitary
binding of TSH to its receptors on thyroid epithelial cells stimulates synthesis of iodine transporter, thyroid peroxidase and thyroglobulin
describe thyroid hormone synthesis
tyrosine is firstly converted into MIT(monoiodotyrosine), which is then converted to DIT (di-iodotyrosine), each reaction uses an iodide, a proton and a molecule of hydrogen peroxide, 2 waste water molecules are produced as biproduct
a molecule of MIT and DIT form T3
2 molecules of DIT form T4
what is structure of T3 and T4
T3 is also known as triiodothyronine, iodines are located 3,5,3’, reverse T3, 3,3’,5’ is biologically inactive
T4 is also known as thyroxine iodine are located 3,5,3’,5’
describe thyroid hormone receptors, describe effect of thyroid hormone on it
T3 receptors are nuclear receptors, expression of these nuclear receptors is very low
free thyroid hormone receptor without bound hormone is bounde to hormone response elements of DNA (HRE) and corepressor (CoR)
after T3 binds receptor CoR is liberative and coactivators bind and transcription begins
describe levels of thyroid hormone in different tissues
thyroid hormone levels vary substantially between organs, T4 content in liver is 10 times higher than skeletal muscles, T3 levels in pituitary gland are very high
difference in hormone levels created by relative blood flow to tissues, rates of T4 and T3 entry and release from cells, amount of intracellular binding sites
how is thyroid hormone metabolised
enzymes used to break down thyroid hormones contain selenium, break off iodine groups
broken down by enzymes D1-3
D1 is not very specific
T4 is broken down into reverse T3 by D3 and D1
reverse T3 is broken down into T2 by D1 and D2
T4 is broken down into T3 by D2 and D1
T3 is broken down into T2 by D3 and D1
D1-3 is contained within all sensitive to thyroid metabolism (most cells)
