The thyroid gland: control of secretion, effects of the thyroid hormones Flashcards

1
Q

Where does thyroid tissue arise from?

A

Midline at a point on the tongue - foramen caecum

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2
Q

In what week do epithelial cells sink downwards anterir to the hyoid and larynx?

A

Week 7

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3
Q

What structure connects the developing thyroid to the tongue?

A

Thyroglossal duct - atophies

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4
Q

What are remnants of the thyroglossal duct called?

A

Thyroglossal cysts

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5
Q

What are the epithial cells which surround the blood vessels in the thyroid called?

A

Follicular cells

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6
Q

What is the sac-like structure lies in the middle of the follicular cells called?

A

Colloid - contains many specialised proteins

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7
Q

What cell types lie between the follicles?

A

Parafollicular C cells

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8
Q

What do para-follicular C-cells release?

A

Calcitonin

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9
Q

What are the follicular epithelial cells involved in?

A

Thyroid hormone synthesis

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10
Q

Where do the small-bodied neurons synthesize and secrete TRH?

A
  • Arcuate nucleus

- Median eminence

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11
Q

Where are the small-bodied axonal terminals located?

A

High up in the pituitary stalk almost in the median emminance itself

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12
Q

Where is TRH released?

A

Capillary network at pituitary stalk (high up) - taken by long portal veins to anterior pituitary where it diffuses on thyrotrophs

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13
Q

Explain the process of TRH on the thyrotrophs and how this results in TSH secretion? (lon flashcard)

A
  • TRH binds to its receptor on cell surface of thyrotrophs
  • TRH receptor is G-protein coupled
  • G protein undergoes confirmational change which induces GDP GTP exchange on the alpha subunit.
  • Alpha sub unit GTP complex falls away from the Beta and gamma sub units of the G protein and the alpha GTP complex activates phospholipase C (PLC)
  • PLC is a membrane assiocated enzyme, hydrolises a phospholipid in the inner leaflet of the membrane
  • Phospholipid is PIP2 - cleaves and yeilds IP3 leaving DAG in the membrane
  • Both IP3 and DAG act as secondary messengers inside cells
  • Ip3 binds to receptor on endoplasmic reticulum which is a calcium channel causes release of calcium from endoplasmic reticulum into cytosol
  • Calcium levels increase above micromolar levels inside cell and activates proteins to exocytose TSH
  • DAG and increased Calcium activates PKC whhich is brought to the membrane by DAG and Calcium
  • PKC phsophorylates a number of proteins that are involved in exocytosis stimulating there activity
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14
Q

What can somatostatin inhibit the release of?

A
  • GH (mainly)

- TSH

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15
Q

What can dopamine inhibit?

A
  • Prolactin

- TSH release

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16
Q

Where does the TSH receptor lie on the follicular cell?

A

Basolateral surface (not facing the colloid)

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17
Q

Explain the process by which TSH stimulates the follicular cells to produce T4 and T3?

A
  • Binds to TSH receptor (G-protein coupled receptor) - interacts with stimulatory G protein (GalphaS)
  • Interacts with Adenylate cyclase which converts ATP into cAMP
  • cAMP acts through acting on protein kinase A also cAMP diffuses into nucleus and activates proteins
  • Slow response by stimulating transcription also
  • Caelease of T3 and T4
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18
Q

Are T3 and T4 hydrophobic or philic?

A

Hydrophobic - able to pass through the lipid bilayer - (may have to be faciliated across membrane)

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19
Q

What are T3 and T4 able to inhibit?

A

Pituitary and hypothalamus (further release of TSH and TRH)

- Also decrease the number of receptors of TRH on thyrotrophs - fur

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20
Q

What are T3 and T4 based on the structure of?

A

Tyrosine

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21
Q

How much more active is T3 than T4?

A

5 - 10 x

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22
Q

What are T3 and T4 derived from what stored molecule?

A

Thyroglobulinm (found in colloid) (exists as a homodimer) (around 330 kilodaltons in size) (~ 120 tyrosines on the amino acid backbone)

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23
Q

What is reverse T3?

A

Inactive T3 - where the inner iodine has been removed

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24
Q

What is thyroglobulin broken down into?

A

Individual amino acids and T4 (and T3)

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25
What cotransorter increases its activity as a result of TSH?
Na/I cotransporter (NIS) (I- and NA+ enter cell) | - Causes increased iodine trapping
26
How much higher is the iodide inside the cell than in the circulation?
40 x
27
What molecule is synthesised as a result of TSH?
Thyroglobulin - then exocytosed to colloid
28
How does Iodide leave the cell into the colloid?
- Via pendrin - Thyroid peroxidase, on the luminal surface of secretory vesicle, oxidises I- to I0 - Chloride goes into cell in response
29
What does the Iodine cause in the colloid?
Iodination of thyroglobulin
30
What is conjugation?
TSH stimulates the conjugation of iodinated tyrosines to form T3 and T4 linked to thyroglobulin
31
What molecule is endocytosed into the cell?
Iodinated thyroglobulin
32
What role does proteolysis play in thyroid hormone secretion?
TSH stimulates the proteolysis of iodinated thyroglobulin, forming T3 and T4 in the lumen of lysoendosomes
33
What is the difference between iodine concentrations in the colloid and the plasma?
millimolar in colloid micro in palsma
34
What hormone causes hyperplasia?
TSH exerts a growth-factor effect on follicular cells of the follicle, stimulating hyperplasia, within thyroid gland, can grow 10x bigger
35
How many iodine molecules are on one tyrosine miolecule usually?
2 (some are monoiodinated)
36
What is the difference in structure between T3 and T4?
T3 has only 1 iodine on the outer ring (T4 has 2 on both inner and outer) rT3 has only 1 iodine on inside
37
What do lysosomes contain?
Proteolytic enzymes
38
What do the proeteolytic enzymes break thyroglobulin into?
- Individual amino acids (T3 and T4) | - Mono and diiodotyrosines that have not been converted to mature T3 and T4 will be recycled, iodine will be removed
39
What are the 2 different types of deiodinase in circulation?
- 5'/3' - monodeiodinase | - 5/3 - monodeiodinase
40
What deiodinase removes iodide atoms from the outer ring?
5'/3' - monodeiodinase
41
What deiodinase removes iodide atoms from the inner ring?
5/3-monodeiodinase
42
What structure is T3 and T4 based off of?
Thyronine (without iodine and sulphate groups)
43
Adding sulphate groups to thyronine allows for what?
Makes them more aqueous and so allows them to be excreted by kidney
44
What does T3 and T4 bind to?
TBG (Thyroxin-binding globulin)
45
What percentage of T3 and T4 is bound to Thyroxin-binding globulin (TBG)?
``` T3 = 99.5% T4 = 99.98% ```
46
What makes cells sensitive to Thyroid hormones?
- Transporter molecules (carrier mediated) | - 3'/5' Monodeiodinase
47
WHat does 3'/5' monodeiodinase do?
Converts T4 to T3 (makes it 5 - 10 x more active)
48
What do the thyroid hormones bind to inside the nucleus?
Thyroid hormone receptor (transcription factor) | - Binds to thyroid response elements
49
What does the thyroid hormone receptor act as a heterodimer alongisde?
Retinoid X receptor (RXR)
50
What vitamin binds to retinoid X receptor?
Vitamin A
51
What is activated when thyroid hormone binds to the Thyroid hormone receptor?
Thyroid response element - DNA starts to unwind which revelas the codon sequence which is transcribed
52
What proteins do Thyroid hormones stimulate to be produced?
- Na+/K+ATPase - Gluconeogenic enzymes - Respiratory enzymes - Myosin heavy chains - Beta adrenergic receptors
53
What is Basal Metabolic Rate (BMR)?
How quickly one uses oxygen to make ATP inside cells
54
By how much can hyperthyroidism increase the BMR by?
Up to 100%
55
By how much can hypothyroidism decrease the BMR by?
50 - 60%
56
What are the physiological actions of the thyroid hormones (e.g on carbohydrate, fat and protein stores)?
- Increased glucose uptake from GI tract - Increased glucose utilisation (especially muscle and adipose tissue) - Increased liver glycogenolysis and gluconeogenesis - Increased lipolysis in adipose tissue (Increased plasma FFA) - General increase in protein turnover with net increase in anabolism - Increase in specific enzymes / membrane proteins / hormone receptors - Permissive actions for other hormones (GH, prolactin, gonadal and adrenal steroids) essential for normal development and function of central and peripheral nervous systems
57
How do goitrogens cause hypothyroidism?
Excess iodine, thiocyanate or pechlorate cause excess TSH secretion and hypertrophy of thyroid and hyothyroidism
58
How does Graves disease cause hyperthyroidism?
Long-acting thyroid stimulator (LATS - autoimmune stimulation of thyroid) - hypertrophy of thyroid and hyperthyroidism
59
How does Hashimoto's disease cause thyroid disorders?
- Autoimmune destruction of thyroid - Antibodies block TSH receptor and destroy follicular cells - Atrophy of thyroid and hypothyroidism
60
What is goitre?
An enlarged thyroid gland - can be hyper or hypothyroidism
61
What is responsible for exopthalmus?
High levels of antibody (not T3 or T4) | - Deposition of mucopolysaccharide behind eye frombinding to TSH receptor on fibroblasts
62
What is severe hypothyroidism known as?
Myxedema