Exam 2 Material Flashcards
What do follicles in thyroid contain?
Cavities
Follicular cells
Parafollicular cells
What kind of cells does parathyroid gland have?
Chief cell
Oxyphil cell
Five functions of thyroid hormones
Important for normal growth and development
Maintain metabolic stability in adults
Have general rather than tissue specific effect
Require dietary iodide for their synthesis
Peripheral tissues convert T4 to T3, providing additional regulatory step of thyroid hormone levels
Role of thyroid hormones in bone
Essential for bone growth and development
Activates osteoclast and osteoblast activities
Deficiency during childhood affects growth
In adult excess thyroid hormone levels associated with increased risk of osteoporosis
Role of TH in cardiovascular system
Has cardiac ino tropic and chronotropic effects
Increases cardiac output and blood volume
Decreases systemic vascular resistance
Role of TH on adipose tissue
Induces white adipose tissue differentiation, lipogenic enzymes, and intracellular accumulation
Stimulates adipocyte cell proliferation
Stimulates uncoupling proteins
Uncoupled oxidative phosphorylation
Role of TH in liver
The regulates triglyceride and cholesterol metabolism, as well as lipoprotein homeostasis. Also modulates cell proliferation and mito respiration.
Role of TH in pituitary
Regulates synthesis of pit. Hormones
Stimulates GH production
Inhibits TSH
TH role in brain
Controls expression of genes involved in myelination, cell differentiation, migration and signaling. Thyroid hormone is necessary for axonal growth and development.
Describe TH mechanism
TH goes to intracellular receptor, transcription of specific gene
Increases protein synthesis, which leads to both cell growth and maturation and and cellular respiration increase.
Cellular respiration leads to increased oxygen consumption and metabolism rate. Cell growth and maturation lead to increased food intake and increased oxygen consumption and metabolism rate. The latter leads to both increased cardiac output and ventilation and increased thermogenesis.
How does thyroxin influence fatty acid release from adipose tissue
If thyroxin binds with epinephrine, it will lead to enhanced release of fatty acids.
Inter follicular connective tissue
Tissue between follicles
What is inside follicles
Colloid
What is inside colloid
Gelatinous thyroglobulin
Difference between over active and under active thyroid epi cell
Under active
Decreased, flattened epi. cells and large colloid reserve
Over active
Tall, columnar epi cells and little colloid (shrunken)
How does TDH stimulate thyroid cells
It stimulates colloid to be endocytosed into cells
How does hormone in thyroglobulin get into bloodstream.
Thyroglobulin is Exocytosis into colloid, where it is iodinated. Then it is endocytosed in colloid droplets that are taken up by lysosomes that digest the thyroglobulin and release the T4 and T3 into the bloodstream
Capillaries into which TH flows are
Fenestrated
What in lysosomes digests thyroglobulin
Acid hydrolases
What receptor does TSH activate
7TM G protein linked receptor
What effects does TSH have on follicular cell
Early effects
Adenylate Cyclase
Endocytosis of colloid
Mito respiration and cell metabolism
Late effects
Iodide uptake
Protein synthesis
DNA replication and mitotic activity
What teo things does TSH receptor activate
Adenylate Cyclase
Phospho lipase C
What does TDH activation of adenylate Cyclase cause
Camp synthesis Transmembrane ion fluxes (sodium, iodine, calcium binds calmodulin) Protein kinase activation Phosphorylation Iodination of thyroglobulin Colloid droplets in cell Cellular metabolism Protein synthesis and rna turnover Iodine in DNA synthesis
Two precursors of thyroid hormones
Monoiodothyrosine
Diiodothyrosine
Which thyroid hormones are biologically acitve? Inactive?
T4 andT3 active
T2 and reverse T3 inactive
Where is T3 synthesized
It is secreted by thyroid, but mostly formed peripherally by T4 deiodination
Iodine pathways
ECF to thyroid and urine Thyroid to ECF and hormone pool Hormone pool to tissues Tissues to Gi tract and iodine pool GI tract to iodine pool and stool
Synthesis and Iodination of thyroglobulin
Amino acids enter for protein synthesis
Incorporate mannose
Incorporate galactose
Through Golgi, send vesicle to Exocytosis to colloid
Iodide enters cell through iodide transporter
Iodide oxidized in cell
Iodide sent to colloid, where it binds with thyroglobulin
Reabsorption and digestion of thyroglobulin
Thyroglobulin endocytosed into cell in colloid droplets that are taken up by lysosome. Acid hydrolase a in lysosome digest droplet and release t4 and T3, which exit into bloodstream through fenestrated capillaries
Size of thyroglobulin
MW660000
How many subunits does thyroglobulin have
Two
How many tyrosine residues does thyroglobulin have
125
How much of thyroglobulin is iodine
One percent
Thyroid peroxidase
TPO
Large MW membrane protein located on apical domain of follicular cells
What two anions block active transport of I ion into epi cell
CLO4-
SCN-
Two transporters on epi basolateral membrane
Na+I- symport
NaKpump
Apical microvilli
Found on apical membrane of follicular cell
What transporter is on apical membrane
Pendrin I-, Cl- transporter (sodium ion independent)
How does TPo iodinate thyroglobulin
Enzyme takes I ion and tyr-protein, binds itself to iodide, binds iodide to protein and recycles itself
What decreases efficiency of TPO
If iodide already bound
How to make T4 or T3
Take two thyroglobulin molecules and TPO
DiIodinate both molecules
Bind them
If only mono iodinate second molecule, becomes T3
Intermediate in t4 synthesis
Quinolone ether intermediate
How does iodine level regulate proportion of T4 and t3
If low levels of iodide, more t3. If not, t4
How does diet regulate levels of t3
T3 decreases with fasting or starvation
This leads to decreased metabolic rate
Calorie conservation
Where is a lot to t4 converted to t3
Liver and kidneys
What do iodothyronine deiodinases contain in their active sites
Selenocysteine
Deiodination site of three deiodinases
1-5’ and 5
2-5’
3-5
Physiological roles of three deiodinases
- Circulate t3’ inactivate t4 and t3, degrade rt3
- Intracellular t3 in pit, brain, brown adipose tissue
- Inactivate t3 and t4
Tissue location of three deiodinases
- Liver, kidney, thyroid, and brain
- Pit, brain, brown adipose tissue, skeletal and cardiac muscle
- Brain, placenta, skin
Substrate preference for three deiodinases
- Rt3>t4>t3
- T4=>t3
- T3>t4
Inhibition by propylthyouracil in the deiodinases
- Sensitive
- Resistant
- Resistant
Response to TH excess by three deiodinases
- Increase
- Decrease
- Increase
Which three proteins bind to TH in circulation
Thyroxin binding globulin
Transthyretin
Albumin (largest, greatest binding capacity)
Thyroxin secretion and feedback mechanism
At hypothalamus
Down, somatostatin and dopamine downregulated TSH release
TRH upregulates it
At pituitary
Glucocorticoids decrease TSH release
Estrogens increase it
At thyroid
TDH upregulates TH release, both, and both bound and free
Bound and free TH downregulate TSH from pituitary
Also downregulate TRH in hypothalamus
Two types of cells in parathyroid
Chief cell
Oxyphil cell
What is in and around follicles of thyroid
Cavity, where colloid is
Follicular cell around colloid
Para follicular cell
Five functions of thyroid hormones
Normal growth and development
Maintain adult metabolic stability
Have general rather than tissue specific effect
Require dietary iodide for synthesis
Peripheral tissues concert T4 to T3, providing addl regulatory steps of thyroid hormone levels
How does TH affect bone 4
- Essential for bone growth and devt
- Activates osteoclast and osteoblast activity
- Deficiency during childhood affects growth
- In adults, excess thyroid hormone levels associated with increased risk of osteoporosis
TH and cardiovascular system 3
- Has cardiac ino tropic and chronotropic effects
- Increases cardiac output and blood volume
- Decreases systemic vascular resistance
TH and adipose tissue 4
- Induces white adipose tissue differentiation, lipogenic enzymes, and intracellular lipid accumulation
- Stimulates adipocyte cell proliferation
- Stimulates uncoupling proteins
- Uncoupled oxidative phosphorylation
TH and liver
TH regulates triglyceride and cholesterol metabolism
Lipoprotein homeostasis
Modulates cell proliferation and mitochondrial respiration
TH and pituitary
Regulates synthesis of pituitary hormones
Stimulates GH production
Inhibits TSH
TH and brain
Controls expression of genes involved in myelination, cell differentiation, migration, and signaling. Thyroid hormone is necessary for axonal growth and development.
Steps for synthesis of thyroid hormone
- Iodide uptake and per oxidation
- Thyroglobulin biosynthesis and secretion into lumen
- Intra colloidal modification of thyroglobulin
- Iodination of tyrosine residues
- formation of iodothyronines by coupling of specific iodothyrosyl residues
Secretion and metabolism steps of TH
- Storage of iodinated thyroglobulin as a colloid
- Endocytosis of iodinated thyroglobulin and fusion with lysosomes
- Cleavage of iodinated thyroglobulin to TH in lysosome
- TH release and metabolism (deiodination)
Of which is there more production? T4 or T3
Twice as much t4 as t3
How much of T3 is made in thyroid? t4
20%, 100%
Distribution of T3 and T4 in liters
T3 40 liters
t4 10 liters
Half life of T3 and T4
t3- 0.75 days
T4- 7.0 days
How does TH affect transcription and protein synthesis
Low dose of T3 given to rat without thyroid
Increase in nuclear RNA
-increase in rRNA and polysome formation
- increase in protein synthesis
How do TH receptors work
Hormone activated transcription factors
What binding domains do TH receptors have
DNA binding
TH binding
Six TH receptors
TRbeta1 TRbeta2 TRbeta3 TRalpha1 TRalpha2 TRalpha3
TRbeta 1 location
Liver, kidney, thyroid
TRbeta2 location
Pituitary, hypothalamus, retina and inner ear
TRbeta3 location
Heart and kidney
TRalpha1 location
Heart, bone and brain
Do TRalpha2 and 3 bind hormone!
No
