M1 L5 Flashcards
1
Q
What is the HPA axis
A
Hypothalamic–Pituitary–Adrenal axis. It’s a key part of your body’s stress response system
2
Q
Explain the flow of the HPT axis
A
1) hypothalamus receives inputs
2) hypothalamus releases TRH
3) TRH stimulates anterior pituitary to release TSH
4) TSH is put into the circulation to stimulate the thyroid gland to produce thyroid hormones
5) T3 and T4 do their thing
3
Q
What does TRH stand for?
A
thyrotropin releasing hormone
4
Q
what is TRH made by? specific
A
made by parvocellular neurons of the paraventricular nucleus (PVN)
5
Q
whats TSH
A
thyroid stimulating hormone
6
Q
What is TSH made by? * by which cells
A
produced by thyrotrope cells in the anterior pituitary
7
Q
What makes T3 and T4
A
Thyroid follicle cells located in the thyroid gland
8
Q
What are follicular cells?
where are
A
protein secreting cells that line the colloid
9
Q
whats a colloid
A
lumen filled with a fluid inside thyroid gland
10
Q
Where is Thyroglobulin found
A
in the colloid
11
Q
What is thyroglobulin
A
a large glycoprotein molecule secreted from follicular cells that acts as a store for thyroid hormone
12
Q
where is the thyroid hormone stored?
A
on the thyroglobulin molecule in colloid
13
Q
What is iodination?
A
The process where iodine binds to tyrosine residues on thyroglobulin.
14
Q
What do C cells make
A
Calcitonin
15
Q
what does TSH do?
A
regulates the thyroid gland’s release and production of T₃ and T₄ by acting on follicular cells through a signaling cascade.
16
Q
What type of receptor is the TSH receptor?
A
A G protein-coupled receptor (GPCR).
17
Q
What is phagocytosed from the lumen by follicle cells?
A
Thyroglobulin (Tg), which contains stored T₃ and T₄.
When the body needs thyroid hormone, follicular cells endocytose (phagocytose) thyroglobulin from the colloid.
18
Q
What are the acute effects of TSH stimulation?
A
- inc Thyroglobulin phagocytosis (thyroid follicular cells are taking in more thyroglobulin from the colloid)
- inc T₃ and T₄ production (bc TSH says so)
19
Q
What are the chronic effects of TSH stimulation?
A
- increased iodide uptake (bc need iodide to make t3/t4)
- increased Tg synthesis
- follicular cell proliferation (cells are multiplying - thyroid gets bigger) LEADS TO GOITER
20
Q
Explain the steps of how thyroid hormone is made and stored using thyroglobulin (Tg)
A
- Tg made in follicular cell
- Secreted into follicle colloid
- Iodinated & conjugates
- Imported by endocytosis
- T3 & T4 break off
(proteolysis) - T3 & T4 enter bloodstream
21
Q
Which step here is regulated by TSH
A
TSH tells the cells to pull Tg back in from the colloid when hormone is needed.
22
Q
Which is more active T3 or T4
A
T3 is the more active form of T4
23
Q
Why can T4 be converted into T3?
A
Because T3 is the more powerful form.
The body can regulate where and when T₃ is made.
24
Q
Which T hormone is more commonly released
A
There is more T4 than T3
25
How do we differentiate between T3 and T4?
T3 has 3 iodines
T4 has 4 iodines
26
What is MIT?
Mono-iodotyrosine (1 iodine added to tyrosine).
27
What is DIT?
Di-iodotyrosine (2 iodines added to tyrosine).
28
How is T₃ formed?
By combining MIT + DIT.
29
How is T₄ formed?
By combining DIT + DIT.
30
How do we go from T3 to T4?
add an iodine
31
What are Deiodonases?
convert T4 into active or inactive forms by removing iodine atoms
32
Deiodinases 3 types:
D1, D2, D3
33
D1 (Dio1)
Tissues:
Preferred substrate:
Function:
Tissues: Thyroid, liver, kidney, pituitary
Preferred substrate: rT₃
Function: Can activate or inactivate thyroid hormones
34
D2 (Dio2)
Tissues:
Preferred substrate:
Function:
Tissues: Thyroid, brain, pituitary, brown fat, placenta, immune cells
Preferred substrate: T₄
Function: Converts T₄ to T₃ (active form)
35
D3 (Dio3)
Tissues:
Function:
Role:
Tissues: Placenta, brain
Function: Converts T₄ to rT₃ or T₃ to T₂
Role: Inactivating hormone → protects tissues from too much thyroid activity
36
What is the iodide trap
It looks for and traps ingested iodide in thyroid follicular cells and sets up a salt gradient to bring it in
37
How does the Iodide trap bring in the iodide?
There is an Na+ gradient set up by the Na⁺/K⁺-ATPase pump.
Then the sodium-iodide symporter (NIS) allows Na+ to go back into the cell and move down its concentration gradient, but only if its accompanied by iodide.
38
Why is the sodium gradient important for iodide transport?
Because Na⁺ wants to enter the cell (down its gradient), and it pulls iodide (I⁻) in with it via NIS.
39
What restores the potassium balance after Na⁺/K⁺ transport?
Voltage-gated K⁺ channels
40
What is a Prohormone?
A prohormone is a precursor to a hormone.
It is inactive or weakly active until it is converted into the active form in a different tissue
41
Which thyroid hormone is the prohormone?
T4 is the prohormone.
42
How does circulation of a prohormone allow for regulation of thyroid hormone effects?
Circulating T4 acts as a prohormone that can be converted into active T3 in target tissues. This allows each tissue to regulate its own thyroid hormone activity based on its specific needs.
43
Steroid pro hormone examples?
Testosterone to DHT
44
Peptide pro hormone examples?
POMC to ACTH to MSH
45
Thyroid hormones need active transporters in and out of the cell. Name those 2:
* monocarboxylate transporters (MCT)
* L-amino acid transporters (LAT)
46
thyroid hormone synthesis:
Where is thyroglobulin (Tg) synthesized, and how does it reach the colloid? (step 1)
Synthesized in follicular cells
Transported into the colloid via exocytosis
47
thyroid hormone synthesis:
How does iodide enter thyroid follicular cells from the bloodstream? (step 2)
Through the Na⁺/I⁻ symporter (NIS)
Uses the Na⁺ gradient to bring in iodide from blood
48
thyroid hormone synthesis:
How is iodide activated once it’s inside the thyroid follicular cell? (step 3)
Thyroid peroxidase (TPO) oxidizes iodide (I⁻) into active iodine (I⁰)
This active form is needed for hormone synthesis
49
thyroid hormone synthesis:
How does activated iodide get into the colloid space? (step 4)
Travels through a luminal channel into the colloid
50
thyroid hormone synthesis:
How is iodide attached to tyrosine residues on thyroglobulin? (step 5)
TPO catalyzes this step
1 iodine → MIT (monoiodotyrosine)
2 iodines → DIT (diiodotyrosine)
51
thyroid hormone synthesis:
What reactions lead to the formation of T3 and T4 hormones? (step 6)
MIT + DIT → T3
DIT + DIT → T4
52
thyroid hormone synthesis:
How are T3 and T4 retrieved from the colloid into the follicular cell? (step 7)
Follicular cells phagocytose Tg from the colloid
This step is stimulated by TSH
53
thyroid hormone synthesis:
What happens to iodinated thyroglobulin inside the follicular cell after phagocytosis? (step 8)
Lysosomes digest Tg
Releases T3 and T4 into the cell
54
thyroid hormone synthesis:
How do T3 and T4 exit the thyroid cell and enter circulation?
T3 and T4 transported into the blood by MCT8 transporter
55
Acute TSH stimulation increases the production of T3 and T4 by promoting which step of 1–9?
Step 7 — TSH stimulates phagocytosis of thyroglobulin (Tg) from the colloid back into the follicular cell.
This brings in Tg containing T3 and T4 → which can then be processed by lysosomes (Step 8) → and secreted into blood (Step 9).
It’s a quick way to release stored hormone when the body needs more thyroid hormone fast.
56
How would thyroid hormone production be altered when iodine is low in the diet? (include total levels & ratio of T3 to T4)
↓ Total thyroid hormone levels – less raw material (iodine) means less hormone can be made overall.
↑ T3:T4 ratio – body favors T3 production since it requires only one less iodine than T4.
57
How do follicle cells respond to prolonged /chronic TSH stimulation (1 point) and how does this alter the size of thyroid gland
Chronic TSH stimulation causes follicular cell proliferation (they grow and divide), which leads to enlargement of the thyroid gland — this is called a goiter.
58
What is Thyroxin-binding globulin:
* affinity?
* plamsa conc
major carrier
* TBG binds:
T4 very tightly bc its being held on for awhile (high affinity)
T3 less tightly bc we need to let it go when its time to use it (lower affinity)
* low bc it has a high affinity - so it doesnt need a huge abundent to do its job
59
What type of receptors are thyroid hormone receptors (TRs)?
Nuclear receptor transcription factors that modulate gene transcription via thyroid response elements (TREs).
60
What happens when thyroid hormone binds to its receptor?
The receptor undergoes a conformational change, releases corepressors, and recruits coactivators to activate gene expression.
61
Where are thyroid hormone receptors expressed?
widespread
62
What do unbound thyroid hormone receptors do?
They stay bound to DNA and suppress transcription by recruiting corepressors.
63
Thyroid hormone effects on metabolism?
Thyroid hormone increases basal metabolic rate ,body heat production, fat mobilization, and glucose in the blood
64
What other things can the thyroid affect?
growth, cardiovascular system (high thyroid = inc HR), CNS (low thyroid = tired), reproductive (low thyroid = infertility)
65
Whats an endemic goiter and why does it occur?
endemic goiter is an enlargement of the thyroid gland
Cause: Iodine Deficiency
* The thyroid needs iodine to make T3 and T4.
* If iodine is low → thyroid hormone levels drop.
Compensatory TSH Increase:
* The pituitary senses low thyroid hormone → releases more TSH.
* TSH stimulates thyroid growth to increase hormone production.
Result: Goiter
66
Graves’ disease:
* what is
* why happen
an autoimmune disorder that causes hyperthyroidism (overactive thyroid).
The immune system makes TSH receptor antibodies (also called TSI – thyroid-stimulating immunoglobulins).
These antibodies mimic TSH and bind to TSH receptors on the thyroid → overstimulating it.
Result = too much T3 and T4 → symptoms of hyperthyroidism.
67
common symptom of graves disease
xophthalmos (puffy, bulging eyes) caused by cellular autoimmune response to TSH-R on adipocytes in orbit of eye
68
Hashimoto’s Disease
* what is
* why happen
an autoimmune disease that causes hypothyroidism (underactive thyroid).
The immune system attacks the thyroid gland, leading to inflammation and gradual destruction of thyroid tissue.
Over time, this damage reduces thyroid hormone production (↓T3 and ↓T4).
69
Hypocalcemia
* what is
* what lead to
low blood calcium concentration can lead to increased neuromuscular excitability and include muscle spasms, tetany (involuntary muscle contractions), and cardiac dysfunction.
70
Hypercalcemia
* what is
* what lead to
high blood calcium concentration can lead to diffuse precipitation of calcium phosphate in tissues, leading to widespread organ dysfunction and damage.
71
What are 5 calcium sources in the body?
1) intracellular calcium
2) calcium in blood and extracellular fluid
3) inside bone (in mineral phase)
4) small intestine (dietary calcium from food)
5) kidney (reabsorbs calcium that enters back into blood)
72
What hormone is secreted when blood calcium levels are low?
* secreted by what?
Parathyroid hormone (PTH), secreted by chief cells of the parathyroid gland.
73
Which cells secrete parathyroid hormone and when are they activated?
Chief cells of the parathyroid gland; activated when plasma calcium is low.
74
What hormone is secreted when blood calcium levels are high?
Calcitonin, secreted by C cells of the thyroid gland.
75
Which cells produce calcitonin and what triggers its release?
C cells (parafollicular cells) of the thyroid; triggered by high plasma calcium.
76
What are the effects of calcitonin?
Inhibits bone resorption
Promotes calcium deposition into bone
Lowers blood calcium levels
77
What are three effects of parathyroid hormone (PTH)?
Stimulates bone resorption
Increases renal calcium reabsorption
Activates vitamin D to enhance gut calcium absorption
78
What type of receptor allows chief and C cells to sense calcium levels?
Calcium Sensing Receptor (CaSR) — a G-protein coupled receptor.
79
How does CaSR regulate PTH in chief cells?
High calcium activates CaSR, which suppresses PTH production and release.
80
How does CaSR regulate calcitonin in C cells?
High calcium activates CaSR, which stimulates calcitonin (CT) release.
81
What second messenger pathway is involved in CaSR signaling?
cAMP (cyclic AMP), via G-protein signaling.
82
What is the primary function of parathyroid hormone (PTH)?
to increase blood calcium levels.
83
How does PTH affect bone?
It mobilizes calcium and phosphate from bone by stimulating bone breakdown.
84
How does PTH affect the kidneys?
It maximizes calcium reabsorption in the tubules, minimizing calcium loss in urine.
85
How does PTH affect vitamin D and the intestine?
It stimulates the kidney to produce active vitamin D, which increases calcium absorption in the small intestine.
86
How does calcitonin affect the kidneys?
It enhances excretion of calcium into urine, helping to lower blood calcium levels.
87
How does calcitonin affect bone?
It inhibits bone resorption, reducing calcium release from bone into the blood.
88
How do the thyroid and parathyroid glands respond to HIGH levels of calcium in the blood. Specify the cell types that are stimulated (1 pt) and inhibited (1 pt) and hormone release changes from the thyroid and parathyroid glands (2 pt)
* high levels of calcium = C cells are stimulated
* C cells release the hormone Calcitonin in response to high calcium?
* the parathyroid cell type inhibited by high blood calcium is chief cells. Also PTH secretion is inhibited
* The thyroid releases more calcitonin to bring calcium down. The parathyroid gland will reduce PTH secretion
