Lecture 5 Flashcards
(17 cards)
Thyroid hormone production
Follows HP axis where hypothalamus secretes Thyroid Releasing Hormone causing the anterior pituitary gland to secrete Thyroid Stimulating Hormone which initiates thyroid hormone synthesis. As opposed to cortisol which is only secreted when need be, we need to have some level of thyroid hormones in our blood even if it’s at a basal level. That is maintained by the tonic release of TRH. But, when the body is under stress e.g cold temp, need to increase metabolism. The pathway is further activated
Thyroid gland
4 cell types: thyroid follicles, colloids, follicular cells and c-cells.
Thyroid follicles = follicular cells (periphery) + colloid (lumen)
communication between colloid cells and follicular cells responsible for T3 and T4 synthesis.
C-cells
secrete Ca regulating calcitonin
T3 and T4
Iodine-containing hormones as they are derived from two tyrosine. Amino acids that are linked with iodine. If three, T3. If four, T4. Follicular cells produce thyroxine (T4) as major hormone which is then converted to T3. hence, thyroxone is precursor of T4 and active T3.
thyroid hormone synthesis
sequential iodination of tyrosine molecule. Once monoiodotyrosine (MIT) and DIT is present in cell, you can either join an MIT and DIT together, or, two DIT molecules. Both can happen, but, combining 2 DIT is preferred as once MIT is made, most of it forms DIT so, increase in substrate availability to combine the DIT molecules and it helps regulate the synthesis of active T3 molecules. If rT3 is formed, it is antagonist to T3
thyroid hormone synthesis STEPS
- synthesis of thyroglobulin in follicular cells and its transport into the colloid. thyroglobulin contains many tyrosine molecules and these tyrosine residues are the sites of iodination
- Iodine (brought in via diet) is transported with Na+ into the colloid space
- Enzymes iodinate the thyroglobulin to make either T3 or T4.
- Through endocytosis, the thyroglobulin T3 T4 complex is brought back to follicular cells
- Vesicles containing complex binds to lysosomes which have a low pH and hydrolyses the complex, allowing for the detachment of T3 and T4 from thyroglobulin and the degradation of thyroglobulin
- T3 and T4 enter circulation
T4
Prohormone, T3 is 10x more biologically active than T4.
Circulating T3
80% from deionisation of T4, 20% from synthesis directly by thyroid gland, decrease metabolic rate.
rT3
100% from deionisation of T4. decrease metabolic rate
thyroid hormone in circulation
Thyroid hormones are amine hormones, however, when in circulation, they act like steroid hormones. Their physical properties allows them to cross the bilayer and once taken up in target cells, they go to the nucleus and activate transcription. For that reason, they are bound to protein to prevent them from degrading. 99.97% T4 are protein-bond is determinent of pathology. Free T3 act by binding to thyroid receptors that regulate gene expression of thyroid responsive gene.
T3/T4 function
They affect nearly every organ in the body.
increase mitochondrial activity and glucose O2 in target cells
increase Basal metabolic rate and heat production
increase normal growth and development
increase cardiac function
hyperthyroidism
thyroid secretes too much hormone causing changes in metabolism, nervous system and the heart. increase O2 consumption rate and metabolic heat production.
increase protein catabolism and may cause muscle weakness
increase heart rate
muscle tremor
Grave’s disease
Graves Disease
Autoimmune disease, body produces thyroid stimulating immunoglobins, mimic the action of TSH resulting in hypersecretion of T3 and T4, enlarging the gland.
-surgery
-B blockers
-Iodine therapy
-Antithyroid
Primary hypotension
could be induced by iodine deficieny. Insufficient thyroid hormone
secondary hypotension
insufficient TSH possibly caused by anterior pituitary tumor
tertiary hypothyroidism
hypothalamus makes insufficient TRH
