Endo 4

Question 1

What do the following hormones use for receptors:

• TRH
• TSH
• T4
• T3

Answer 1

TRH- Gq-linked receptor [IP3]
TSH-G-linked receptor [cAMP] and Gq-linked receptor [IP3]
T4- ?
T3-nuclear receptor

Question 2

TRH synthesis and release and inhibitory influence

Answer 2

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

Question 3

TSH synthesis and release

Answer 3

TRH interacts with Gq linked receptor
Activates phospholipase C and IP3 formation
Increased TSH alpha/beta gene expression
Release of TSH granules

Question 4

Hormone synthesis by the thyroid gland

Answer 4

• 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

Question 5

Hormone release

Answer 5

endocytosis of iodinated Tg

proteolysis of the TgI to release the thyroid hormones

Question 6

Two oxidation steps occur in the lumen; both use TPO explain these steps

Answer 6

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

Question 7

Thyroid regulation by TSH

Answer 7

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

Question 8

Circadian rhythm secretion of thyroid hormones has secretion highest between?

Answer 8

10am and 2pm

Question 9

What is the wolff-chaikoff effect?

Answer 9

Autoregulation

An excess of iodide inhibits the activity of iodide trapping

Question 10

What is the T4:T3 secretion ratio?

Answer 10

4:1

Question 11

What is the T4:T3 ratio in the plasma?

Answer 11

20:1

Question 12

How are circulating thyroid hormones found?

Answer 12

Bound to thyroxin-binding globulin

Question 13

Explain T3 delivery in the cell

Answer 13

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

Question 14

Activated receptors may

Answer 14

enhance or suppress gene expression

Question 15

What are the four isoforms identified of TRs

Answer 15

alpha 1 and 2

beta 1 and 2

Question 16

Deiodination of thyroid hormones occurs in?

Answer 16

liver
kidney
brain
muscle

Question 17

Physiological actions of thyroid hormones

Answer 17

regulate metabolic rate (glucose consumption in cells) and thermogenesis (calorigenic hormones)
Appropriate levels of T3 also essential for normal cardiac function

Question 18

Terminal brain differentiation and thyroid hormones

Answer 18

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

Question 19

Other effects of thyroid effects

Answer 19

• needed for normal hematopoiesis

- needed for normal gonadal development and function, including the seasonality of reproduction

Question 20

Maternal hypothyroidism

Answer 20

TH deficiency may lead to congential hypothyroidism or cretinism

Question 21

Hypothyroidism and causes

Answer 21

• 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

Question 22

Hyperthyroidism

Answer 22

Levels of thyroid hormones in the blood are excessively high
Weightloss, nervousness, excessive sweating, protruding eyes

Question 23

Euthyrid sick syndrome (ESS)

Answer 23

Non-thyroidal condition characterized by low circulating T3 and T4 leveles and high rT3
-surgery, radiation/chemotheramy