Thyroid Axis Flashcards
(30 cards)
Hormone Synthesis
- uptake of iodide by thymocytes
- synthesis of the protein, thyroglobulin by the thyrocytes
- Exocytosis of Tg to the follicular lumen
- Iodination of the Tg in the lumen
Hormone release
- endocytosis of iodinated Tg (TgI)
- proteolysis of the TgI, releasing the thyroid hormones
2 oxidation steps occurs in the lumen — both use TPO!
Step 1: TPO iodinates tyrosine residues in the Tg to form mono- and diiodinated tyrosine residues [(MIT) and (DIT); mono- and diiodotyrosines]
Step 2: TPO causes the condensation of MIT and DIT residues to form triiodothyronine (T3) and tetraiodothyronine (T4)
• These iodinated thyronine residues remain as part of the Tg molecule
Thyroid regulation by TSH
- TSH receptors are G-protein linked
- Some are αs and some αq; activation of both lead to cAMP and IP3/DAG production
- Combined actions of the two receptor types regulate almost all aspects of thyroid hormone synthesis and release
Regulation of Secretion
Pulsed secretion of TRH; highest between 10AM-2PM (Circadian)
Wolff-Chaikoff Effect (auto regulation)
an excess of iodide (>2 mg/day) inhibits iodide “trapping”
Humans/dogs secrete T4:T3 at _____ ratio; more ____ secreted only in hyperfunction
4:1; T3
_____________ of T3 produced by peripheral conversion from T4 in the liver and kidneys (& brain)
60-75%
T4:T3 ratio in plasma 20:1 — why?
Boils down to elimination — 1/2 life! (T3 is eliminated much faster than T4)
Transport of TH’s
- > 99% of thyroid hormones in blood circulation bound to thyroxin-binding globulin (TBG) (small!)
- Only free fractions of thyroid hormones biologically active
T3 binds to hormone receptors in the __________ of target cells and regulates the expression of various genes
Nucleus
T4 may bind to ___________________ on the cell membrane and activates intracellular events that bring about rapid responses
G-protein coupled receptors
*activated receptors may enhance or suppress gene expression
Four isoforms of the TR’s are known…
- alpha 1 and 2; beta 1 and 2
*distribution is tissue specific and age dependent
* can form dimers w/ one another and still activate the gene
T4 1/2 life __________; T3 1/2 life ________
6-7 days; 1 day
Deiodination of thyroid hormones occurs in _______, ________, __________ and ___________; sequential removal of iodide to form thyronine
Liver; kidney; brain; muscle
Conjugation of thyroid hormones occurs in the _________, excretion (to prevent hyperthyroidism) via ________ and via the _____________
Liver; bile; kidney
Physiologic Action
- permissive; collaborate with other hormones
- Involved in the synthesis of other hormones
- Enhances the effects of GH
- Regulate metabolic rate and thermogenesis
- Essential for normal cardiac function
Maternal Hypothyroidism
- may lead to congenital hypothyroidism or cretinism
- stunted physical and impaired mental development due to untreated prenatal deficiency of thyroid hormones
- Mental retardation, swelling of the skin, loss of water and hair, bone thinning, delayed puberty; female ovulation issues and infertility
____ is essential from normal development of bones and CNS of growing fetus
T3
Thyroid hormone-dependent development of the brain begins ____________, completed after birth
In utero
T4 is delivered to the ______________ where it is converted to T3
Fetal brain
Hypothyroidism
- abnormally low serum levels of thyroid hormone
- slows metabolic processes throughout the body
- May cause fatigue, slow heart rate, and dry skin
T3 regulates…
T3 is needed for…
T3 substantially increases…
- dendritic and axonal growth
- myelin formation
- synapsis formation
- neuronal migration
- normal hematopoiesis
- normal gonadal development and function, including seasonality of reproduction in seasonal breeders
- K+/Na+ pump activity
- # and activity of mitochondria
- ATPase activity
Causes of Hypothyroidism
- Insufficient dietary iodide (main cause)
- Anti-thyroid factors in diet (goitrogens)
- Mutant TSH-R or TRH-R (genetic)
- TSH deficit
- Mutant TH transport proteins
- Impaired TH synthesis
- Peripheral resistance to TH
- Thyroiditis (Hashimoto)
