Thyroid Hormone - Final Exam Flashcards
1
Q
Whats makes up thyroxin?
A
2 tyrosines with ether link and iodine
2
Q
T4
A
Thyroxin
3
Q
How many iodine does T4 have?
A
4
4
Q
What is the active nuclear hormone?
A
T3
5
Q
What is a thyroid hormon non-nuclear effect?
A
Ion channels at the membrane
6
Q
Where does TH get its iodine from? (2)
A
- Diet
2. Environment
7
Q
What is one of the most common hormone disease?
A
TH disease
8
Q
Where is TH important for development? (2)
A
- Brain
2. Skeletal
9
Q
What is an example of an animo acid derivative?
A
Thyroxine (T4)
10
Q
How can radioactive iodine enter into the body? (2)
A
- Ingestion
- Inhalation
- It dissolves in water so its easy to move from the atmosphere to humans
11
Q
What is the effects of normal TH? (5)
A
Normal…
- Fetal
- Child growth
- Brain development
- Basal metabolic rate
- Metabolism
12
Q
What 2 hormones do you need to have proper development?
A
- Growth hormone
2. Thyroid hormone
13
Q
What is the most common endocrine disease?
A
TH disease
14
Q
What is the cause of hypothyroid?
A
Too little TH
15
Q
What is the cause of hyperthyroid?
A
Too much TH
- Over active thyroid gland
16
Q
Does TH disease affect more men or women? Why?
A
Women (1/7)
- Because of the demands of pregnancy and the monthly cycle (estrogen changes)
17
Q
What has plasticizers shown to do?
A
Shown to bind to TH receptor and have a selective effect on its function
18
Q
What kind of TH disease is common in cats? How does this effect weight?
A
Hyperthyroidism
- Burns up energy too rapidly and typically suffers weight loss even when having an increase in appetite and food intake
19
Q
What kind of TH disease is common in dogs? How does this effect weight?
A
Hypothyroidism
- Gains weight while only eating moderately
20
Q
Where does thyroid originate?
A
From the pharynx
21
Q
What is the thyroid made up of? And what are they lined with?
A
- Sacs called follicle cells
- Lined with epithelial cells
22
Q
How does TH get to the blood?
A
Through capillaries
23
Q
What is the thyroglobulin large precursor protein called?
A
Colloid
24
Q
What adds iodine?
A
Thyroid peroxidase
25
TPO
Thyroid peroxidase
26
What is thyroid peroxidase?
It is a membrane bound glycoprotein enzyme that sticks out into colloid
27
Where does thyroglobulin go after it gets degraded?
It is free and TH get released into blood on the other side of the cell
28
TH synthesis (10 steps)
1. Uptake of iodine (active transport across basement membrane)
- Iodine is the oxidized by TPO so it can attach to TG
2. Uptake of amino acids and sugars
- occurs at the base of the cell from the capillaries
3. Production of TG
4. Packaging of TG by golgi conplex
5. Secretion TG into colloid by exocytosis at aprical surface of cells
6. Production of iodinated TG
7. TG with its iodinated tyrosines is stored in the colloid
8. In the same or neighbouring cell, TG reabsorbed at appropriate time
- stimulated by TSH
9. Lysosome fuse with endosome and TG digested
10. THs are released into capillaries at bottom of cells
29
TG
Thyroglobulin
30
I-
Iodide
31
What is the main form of iodide you eat?
Iodized salts
32
Where is iodide taken up and distributed?
- Taken up by the intestines
| - Distributed to the extracellular fluid
33
Where is iodide distributed?
Extracellular fluid
34
What clears iodide?
The kidneys
35
What happens to the thyroid gland if lacking iodide?
The thyroid gland is not secreting TH and it gets enlarged
- lack of negative feedback loop by TH so TSH keeps pumping up the thyroid gland causing goitre (signs of underlying diseases)
36
What kind of uptake relationship does iodide and thyroid activity have?
- Inversely proportional
| - Directly proportional
37
How do you treat an overactive thyroid?
By giving it a low does of radioactive iodine to kill the thyroid cells
38
How do you treat thyroid cancer?
By giving is a high does of radioactive iodine to kill the thyroid cells
39
What does too much iodide cause?
Down-regulation of TH
40
Which thyroid hormone is more and less active?
- More = T4
| - Less - T3
41
What can deiodinase mimic? (2)
1. Testosterone
| 2. Estrogen
42
What happens when deiodinase removes an iodide from the outer ring?
It activates it
43
What enzyme is used to remove iodides from deiodinase outer ring?
5'-deiodinase
44
What happens when deiodinase removes an iodide from the inner ring?
It deactivates it
45
What enzyme is used to remove iodides from deiodinase inner ring?
5-deiodinase
46
What is thyroxin more associated with?
Blood
47
Where is T3 made?
In the membrane of the cell and is then brought into the cell
48
T3
Triiodothyronine
49
What 3 types of TH are not active in the nucleus?
1. T1
2. T2
3. rT3
50
T1
Monoiodothyronine
51
T2
Diiodothyronine
52
What are 4 physiological importances of deiodinases?
1. Permit local tissue modulation of TH
- form of regulation
2. Assist organism adopt to changing states
3. Regulate TH actions in development
4. Most T4 is metabolized by deiodination to T3 or rT3, remaining inactivated in live or kidney
53
Where does inactive TH remain? (2)
1. Liver
| 2. Kidneys
54
What is sulfation?
The process of adding groups to make THs more hydrophobic so they can pass the membrane more easily
55
What cells make up thyrotrophs?
Anterior pituitary cells
56
What to thyrotrophs release?
TSH
57
TSH
Thyroid stimulating hormone
58
What does TSH cause? (3)
1. Increase in thyroid gland size
2. Increase in thyroid vascularization
3. Stimulation of the thyroid gland function
59
TH axis/regulation steps (5)
1. Neurons from hypothalamus secretes TRH into portal veins that provide a direct route for TRH to the anterior lobe cells
2. Thyrotrophs in the anterior pituitary are stimulated by TRH and secrete TSH into the pituitary venous system
- inhibited by somatostatin from hypothalamus
3. Follicular cells in thyroid are stimulated by TSH and secrete TH into the capillaries for transport to target tissues or via blood stream back to the hypothalamus and pituitary
4. TH transported into cells to target tissues
- In the nucleus TR/T3 binding to TREs regulates genes via transcription up or down
5a. Negative feedback: Serum T3 and T4 levels regulate TRH and TSH
5b. Negative feedback: excess iodide inhibits
60
TRE
Thyroid response element
61
What 2 factors stimulate TRH?
1. Circadian rhythm
| 2. Cold
62
What inhibits TSH? (2)
1. Glucocorticoids
| 2. Chronic illness
63
What can either stimulate or block TH regulation?
Autoimmune Ab TSH receptors on the thyroid
64
What does TSH stimulate? (3)
1. Follicle growth
2. TH synthesis
3. TH secretion
65
Is TH hydrophobic or hydrophilic?
Hydrophobic
66
What does TH need in order to cross the membrane?
Needs transport proteins in hydrophilic blood
67
What is a good source of TH and why?
- Blood binding protein
| - Cause it binds tightly and keeps it stable
68
TBG
Thyroid binding globulin
69
What tightly binds T3 and T4?
Thyroid binding globulin
70
What is TBG deficiency?
- Is a genetic condition that typically does not cause any health problems. Thyroxine-binding globulin is a protein that carries hormones made or used by the thyroid gland
- Reaches equilibrium of free TH, but low total TH since Th is not stabilized so its degraded quickly
71
What is the result of thyroid binding globulin deficiency?
Hypothyroidism
72
What is the half life of TH in the plasma?
7 days
73
What does T4 bound to blood binding proteins do?
Can store it for later use
74
THBP
Thyroid hormone binding proteins
75
What does TH bind to?
Cytoplasmic THBP
76
What are THBP?
They are multifunctional proteins that bind TH with ranging affinities
77
What are the 3 domains nuclear receptors have?
1. Amino terminal domain
2. DNA binding domain
3. Ligand binding domain (at C terminal)
78
What does a mutation in the ligand binding domain cause?
TH resistance
79
What are 2 important differences from steroid receptors to thyroid receptors?
1. TRs dont use heat chock proteins
| 2. TRs stay bound to DNA in the nucleus
80
What is the difference between a ligand and a receptor?
- Ligand is a general term for any molecule that binds to another molecule
- Receptor is a protein to which a signalling molecule that binds specifically and stimulates a particular response by a cell
81
What are the 2 zinc fingers functions? (2)
- 1 zinc finger binds DNA
| - The other zinc finger is used for dimerization
82
How do the 2 zinc bind to zinc?
Through cysteine residue (- charge)
83
HRE
Hormone response element
84
Where does specificity come from in the hormone response element? (5)
1. Timing
- receptor expression/ hormone signal
2. Context
- cell type, surrounding sequence
3. Cofactor expression/activation
4. Exact spacing
5. Sequence of HRE
85
What does TR binds as?
A heterodimer, preferentially with RXR
86
What do half sites bind as?
Homodimers
87
What makes up a homodimer?
2 thyroid receptors
88
What makes up a heterodimer?
1 thyroid recetor and 1 retinoic X receptor
89
What do transcription complexes do? (2)
1. Bind
| 2. Stabilize
90
How do receptors bind to DNA?
As dimers without hormones
91
When do hormones bind and what happens?
- Hormones bind later
| - It changes and activates its state
92
What does it mean if the receptor cant bind to the DNA or ligand?
Its an antagonist
93
What happens if the TRE is positive?
Then TR repressing along, and the ligand TH binds and together activating
94
What happens if the TRE is negative?
TR can be activating without TH and repressing with TH
95
Corepression and coactivation of nuclear receptors steps (3)
1. Corepressor complex: histone deacetylases (HDACs) close chromatin, repressing transcription
- acetyl groups is bulky and removes the positive charge on the histone to decrease the interaction with a negative phosphate on the DNA
2. Ligand binds and ATP is used to remodel the chromatin
3a. Coactivators recruit histone acetyltransferases (HATSs), it opens up chromatin for transcription
3b. Large coactivator complexes for TR bridge with basal transcription machinery
- eg) TATA binding protein and other general TF
96
HAT
Histone acetyltransferase
97
What 2 factors are important for remodelling and development? What are 3 examples?
1. Proliferation
2. Apoptosis
- -> creates turn over
1. TH causes increase transcription of caspases of caspases for apoptosis
2. Caspase 3 and cyclins for proliferation
3. Cyclin D to move to S phase for DNA synthesis
98
What happens if you mess with proliferation and apoptosis?
Leads to diseases
99
What 2 factors increase due to TH?
1. Proliferation
| 2. Apoptosis
100
What do cyclins help with?
Going through the cell cycle
101
What are many cellular pathways and functions regulated by?
TH
- 25 upregulate
- 50 downregulate
102
What can TR beta do?
Autoregulate
| - represses without ligand and then activates itself
103
What 2 factors are upregulated by TR beta?
1. TR alpha
| 2. 5'-deiodinases
104
Do nuclear receptors have non-genomic and/or genomic features?
- Non-genomic = no
| - Genomic = yes
105
Does timing have non-genomic and/or genomic features?
- Non-genomic = rapid (secs-hours)
| - Genomic = slow enough for transcription (2hrs+)
106
Do TH forms have non-genomic and/or genomic features?
- Non-genomic = All forms of TH
| - Genomic = T3
107
Does amplitude have non-genomic and/or genomic features?
- Non-genomic = small (1 to several fold)
| - Genomic = Huge (multifold)
108
Does signal transduction have non-genomic and/or genomic features?
- Non-genomic = Yes
| - Genomic = No
109
What are intergrins?
They are receptors that mediate attachment between a cell and other cells of the extracellular matrix
110
What does rapid intracellular effects include? (5)
1. Ion flux
2. Translation efficiency in ER
3. Mitochondria activity (especially in the liver)
4. Glucose and amino acid uptake
5. Actin polymerization (remodelling, neural connections, cell movement, intracellular trafficking, muscle contraction, pseudopod formation, ect)
111
What are 5 examples of TH non-genomic effects?
1. Calmodulin
2. Integrins
3. PIP3
4. cAMP
5. Protein kinase
112
How does T3 enter the cell?
By specific transporters
113
What does T3 act in once it enters the cell? Via?
Acts in the nucleus via TR
114
What doe T3 act directly on?
Ion channels at the membrane
115
What action does TH have on cardiac myocytes?
Increases heart rate
116
How can TH affect TR in the nucleus?
Through phosphorylation cascades
117
What happens when TR is phosphorylated?
It is activated and its co-repressed proteins are dissociated
118
CDK
Cyclin dependent kinase
119
MAPK
Mitogen activated protein kinase
120
HDAC
Histone deacetylase
