Endo 4 Flashcards
What do the following hormones use for receptors:
- TRH
- TSH
- T4
- T3
TRH- Gq-linked receptor [IP3]
TSH-G-linked receptor [cAMP] and Gq-linked receptor [IP3]
T4- ?
T3-nuclear receptor
TRH synthesis and release and inhibitory influence
stimulatory control:
-alpha 1-adrenergic nerves stimulate pre-pro TRH gene expression and pulsatile release of TRH
Inhibitory influence:
physiological levels of T4 inhibit pre-proTRH gene expression and TRH release
TSH synthesis and release
TRH interacts with Gq linked receptor
Activates phospholipase C and IP3 formation
Increased TSH alpha/beta gene expression
Release of TSH granules
Hormone synthesis by the thyroid gland
- uptake of iodine by thyrocytes
- synthesis of the protein Tg, by thyrocytes
- exocytosis of Tg to the lumen of follicles
- iodination of the Tg in the lumen
Hormone release
endocytosis of iodinated Tg
proteolysis of the TgI to release the thyroid hormones
Two oxidation steps occur in the lumen; both use TPO explain these steps
step 1: TPO iodinates tyrosine residues in the Tg to form mono and diiodinated tyrosine residues and diiodotyrosine
step 2: TPO causes the condensation of MIT and DIT residues to form T3 and T4
Thyroid regulation by TSH
TSH receptors are G-protein linked
Some are alpha s and some alpha q- activation of both leads to cAMP and IP3 production
-combined actions of the two receptor types regulates almost all aspects of thyroid hormone synthesis and release
Circadian rhythm secretion of thyroid hormones has secretion highest between?
10am and 2pm
What is the wolff-chaikoff effect?
Autoregulation
An excess of iodide inhibits the activity of iodide trapping
What is the T4:T3 secretion ratio?
4:1
What is the T4:T3 ratio in the plasma?
20:1
How are circulating thyroid hormones found?
Bound to thyroxin-binding globulin
Explain T3 delivery in the cell
T3/T4 are lipid soluble so they cross cytoplasmic membrane and bind to receptors
The nuclear receptor bind the DNA as heterodimer
-tyroid hormone receptor (TR) makes up one part of the heterodimer
-RXR receptor makes up the other (Vit A derivative)
-once bound the two parts of the heterodimer can bind to DNA to facilitate
Activated receptors may
enhance or suppress gene expression
What are the four isoforms identified of TRs
alpha 1 and 2
beta 1 and 2
Deiodination of thyroid hormones occurs in?
liver
kidney
brain
muscle
Physiological actions of thyroid hormones
regulate metabolic rate (glucose consumption in cells) and thermogenesis (calorigenic hormones)
Appropriate levels of T3 also essential for normal cardiac function
Terminal brain differentiation and thyroid hormones
T3 is essential for normal development of bones and CNS
Thyroid hormone dependent development of the brain begins in utero, completed after birth
Maternal TH’s first supply the needs of the embryo/fetus
T4 is delivered to the fetal brain where it is converted to T3
Dendritic and axonal growth, myelin formation and synapsis formation as well as neuronal migration are regulated by T3
Other effects of thyroid effects
- needed for normal hematopoiesis
- needed for normal gonadal development and function, including the seasonality of reproduction
Maternal hypothyroidism
TH deficiency may lead to congential hypothyroidism or cretinism
Hypothyroidism and causes
- Serum levels of TH’s are abnormally low
- fatigue, slow heart rate, dry skin
- insufficient dietary iodide, anti-thyroid factors in diet, mutant TSH-R orTRH-R
- Mutant TH transport proteins
- imparied TH synthesis
Hyperthyroidism
Levels of thyroid hormones in the blood are excessively high
Weightloss, nervousness, excessive sweating, protruding eyes
Euthyrid sick syndrome (ESS)
Non-thyroidal condition characterized by low circulating T3 and T4 leveles and high rT3
-surgery, radiation/chemotheramy
