Thyroid Hormone Synthesis Flashcards

1
Q

location of thyroid gland

A

below larynx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

thyroid structure

A

2 lobes in each side of trachea. A narrow band (isthmus) connects the 2 lobes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

blood supply to thyroid

A

superior thyroid artery (from external carotid)and inferior thyroid artery (from thyrocervical trunk of subclavian)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T/F thyroid receives highest blood flow of all endocrine organs

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

functional unit of thyroid

A

follicle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

follicle structure

A

layer of cells surrounding lumen filled with colloid. Colloid mostly made of thyroglobulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

types of cells in thyroid

A

follicular (surround colloid) and parafollicular cells (C cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

role of parafollicular cells

A

parafollicular cells found between follicles and secrete calcitonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

ingredients for thyroid hormone synthesis

A

Iodide and tyrosine; Thyronine is the backbone of the THs, and the 3, 5, 3’, 5’ positions can be iodinated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

thyroid hormones

A

Thyroxine (4 iodides) and triiodothyronine (3 iodides attached)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Iodide transport

A

ingest iodine from food– iodide absorbed from gut to enter blood/extracellular iodide pool– exits pool into follicular cells, difuses from basolateral to apical side and exits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

where does organification of iodide occur

A

this occurs at follicular cell-colloid interface (must be oxidized before it can participate in tyrosyl iodination)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

enzyme catalyzing iodination of thyroglobulin

A

thyroperoxidase; membrane bound glycoprotein in microvilli of apical membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Thyroglobulin

A

glycoprotein made on RER within follicular cells and transported to golgi for glycosylation and packaging. Secretory vesicles released from apical side to lumen where TG enters colloid

  • all iodination and coupling reactions of TH synthesis occur on tyrosyl residues of TG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Thyroid hormone synthesis

A

thyroperoxidase catalyzes iodination of tyros)l moieties on TG to form monoiodotyrosine and diiodotyrosine (MIT and DIT) on TG. 2 DITs or 1 DIT and 1 MIT couple to form iodothyronines, thought to be catalyzed by thyroperoxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

iodination inhibitors

A

inhibit iodination, causing decreased TH synthesis and secretion, which causes elevated TSH and gland hypertrophy (GOITER)

  • thiourea drugs (propylhiouracil-PTU) and methimazole
  • aka goiterogens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

thyroid hormone secretion

A

Drops of colloid move into follicular cells via endocytosis and coalesce with lysosomes. Lysosomal enzymes cleave T4 and T3. Much more T4 than T4 (about 20x)

  • DIT and MIT can also be cleaved, but these will be deiodinated and tyrosine/iodine reincorporated into TG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

thyroid hormone transport

A

most protein bound (99.9%) and some in free form (.03% T4 and 0.3% T2)
- Free form is active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what proteins bind TH in blood

A

thyroid binding globulin (TBG), thyroid-binding pre-albumin (TBPA) and albumin
- about 30% of sites occupied by TH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

role of protein bound TH

A

acts to delay, buffer, and prolong TH action; more pronounced for T4 than T3, partly since proportionally more T4 is bound due to higher affinity of TBG for T4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

which thyroid hormone has faster onset of action

22
Q

which thyroid hormone has shorter half life

A

T3 (7 days vs 1 day)

23
Q

which TH more active

A

T3 considered active form due to increased affinity of TH receptor for T3

24
Q

how do TH act

A

T3/T4 enter cells via active transport. T4 converted to T3 via 5’deiodinase. T3 enters nucleus and interacts with nuclear receptors. T3-receptor complex acts on DNA to direct transcription of mRNAs. (eg. NA-K ATPaseaka the Na-K pump, and respiratory enzymes stimulated)

25
actions of TH
1. regulate metabolic rate- most of calorigenic effect due to Na pumping. Evident in most tissues except spleen, brain, testis. More hormone = more basal heat production/O2 consumption 2. Fetal and neonatal brain development (proliferation, differentiation, myelinogenesis, neurite outgrowth, synapse formation) 3. normal growth 4. enhance response to catecholamines== mimic effects of sympathetic nervous system activation 5. Affect metabolism- time and dose-dependent. Low to mod dose tend to be anabolic, while high doses catabolic -- increased fuel consumption, protein breakdown, muscle wasting, lipolysis. Low-mod doses promote conversion of glucose to glycogen; high doses enhance glycogenolysis
26
TH synthesis/secretion control
TRH form hypothyroid acts on membrane receptor in pituitary thyrotrophs, causing increased cAMP and hydrolysis of phosphatidyl inositol. stimulates thyrotrophs in pituitary to release TSH, which is carried by blood to thyroid - TSH acts on membrane receptor to stimulate thyroid hormone synthesis (stimulates iodide pump (with latency), thyroperoxidase and endocytosis of colloid) - TSH increases iodide organification, coupling of iodotyrosines, TG synthesis, and TG proteolysis following endocytosis from colloid. Causes increased release of TH secretion-- thought to me mediated by cAMP - Also affects gland morphology -- follicular cells proliferate, enlarge, elongate and compensatory changes in colloid amount Free T3/T4 influence response of anterior pituitary to TRH (high levels reduce response, while low sensitizes the response)
27
How does TSH interact with tyroid receptors
Thought to be mediated by cAMP. TSH activates adenylate cyclase by binding to receptor on follicular cell membrane - increasing evidence of other second messengers participating in TSH stimulation
28
mechanism for iodide transport into gland
"iodide trap" mechanism - trap refers to fact that membrane pump on basal side promotes accumulation of concentration of iodide in thyroid about 30-40x serum. Iodide concentrated in gland against electrical and chemical gradient - certain anions (ClO4) transported same mechanism and act as competitive inhibitors of iodide uptake
29
is iodide moving with/against gradient when exiting follicular cell on apical side
with chemical and electrical gradient
30
what needs to happen to iodide before iodinating tyrosyl
have to oxidize
31
enzyme catalysing iodination of thyroglobulin
thyroperoxidase
32
what enzyme converts T4 to T3
5'-deiodinase
33
what happens in iodine deficient diets
eventually get decreased TH synthesis/secretion
34
what happens with high iodine doses
short term-- elevated iodide leads to decrease TH release -- called Wolff-Chaikoff effect
35
Wolff-Chaikoff effect
when you have high doses of iodine, short term the elevated iodide will also cause decreased TH synthesis - underlying mechanism involves decreased incorporation of iodide into TG and consequent TH synthesis - high iodide diminishes response to TSH - high iodide diminishes response to TSH
36
when is high iodine intake used
can be used for preparing patients for thyroid surgery
37
consequence of excessive iodine intake
hypothyroid; iodine will inhibit TH release (Wolff-Chaikoff effect)
38
consequence of too little iodine intake
hypothyroid
39
do you use iodine for chronic hyperthyroid management
no; effects are transient
40
three main control mechanisms for TH synthesis/secretion
TSH levels, Iodide, "others" (ions that inhibit uptake from blood)
41
what molecules/drugs inhibit thyroid hormone synthesis and secretion
perchlorate and thiocyanate (found in cabbages and cassava - Drugs: propylthiouracil and methimazole can block TPO activity and thus incorporation of iodide to form TH; also block T4 to T3 conversion in target cells of the thyroid
42
what are some stimuli that alter TRH release
cold, fasting, stress
43
control of TSH secretion
negative feedback. increasd levels of T3 adn T4 feed back to inhibit release of TSH. Unsure if they also inhibit secretion of TRH
44
what molecule used as index of thyroid function
TSH since it is difficult to accurately assess free TH levels
45
excess TH
hyperthyroidism
46
conditions of excess TH
Graves disease (autoimmune), tumors of pituitary or thyroid, excess TH administration
47
Conditions of deficiency of TH
Hashimoto's thyroiditis, iodine deficient diet (in child = cretinism)
48
cretinism
deficiency of iodine in diet | - severe mental and growth retardation
49
signs and sxs of excess TH
BMR, nervous, pretibial myxedema (Graves), heat intolerance, muscle weakness, Goiter, palpitations, exopthalmos (Graves), lid retraction (Graves), Tachycardia
50
signs and sxs of TH deficiency
BMR lower, lethargy, weak, myxedema, cold intolerance, slow speech, goiter, hoarseness, mental slowness, psychosis, bradycardia
51
most common cause of hypothyroidism in US
Hashimoto's thyroiditis
52
most common cause of hypothyroidism worldwide
iodine deficient diet