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MD4001 Physiology > The thyroid gland: control of secretion, effects of the thyroid hormones > Flashcards

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
Q

What cotransorter increases its activity as a result of TSH?

A

Na/I cotransporter (NIS) (I- and NA+ enter cell)

- Causes increased iodine trapping

26
Q

How much higher is the iodide inside the cell than in the circulation?

A

40 x

27
Q

What molecule is synthesised as a result of TSH?

A

Thyroglobulin - then exocytosed to colloid

28
Q

How does Iodide leave the cell into the colloid?

A
  • Via pendrin
  • Thyroid peroxidase, on the luminal surface of secretory vesicle, oxidises I- to I0
  • Chloride goes into cell in response
29
Q

What does the Iodine cause in the colloid?

A

Iodination of thyroglobulin

30
Q

What is conjugation?

A

TSH stimulates the conjugation of iodinated tyrosines to form T3 and T4 linked to thyroglobulin

31
Q

What molecule is endocytosed into the cell?

A

Iodinated thyroglobulin

32
Q

What role does proteolysis play in thyroid hormone secretion?

A

TSH stimulates the proteolysis of iodinated thyroglobulin, forming T3 and T4 in the lumen of lysoendosomes

33
Q

What is the difference between iodine concentrations in the colloid and the plasma?

A

millimolar in colloid micro in palsma

34
Q

What hormone causes hyperplasia?

A

TSH exerts a growth-factor effect on follicular cells of the follicle, stimulating hyperplasia, within thyroid gland, can grow 10x bigger

35
Q

How many iodine molecules are on one tyrosine miolecule usually?

A

2 (some are monoiodinated)

36
Q

What is the difference in structure between T3 and T4?

A

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
Q

What do lysosomes contain?

A

Proteolytic enzymes

38
Q

What do the proeteolytic enzymes break thyroglobulin into?

A
  • 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
Q

What are the 2 different types of deiodinase in circulation?

A
  • 5’/3’ - monodeiodinase

- 5/3 - monodeiodinase

40
Q

What deiodinase removes iodide atoms from the outer ring?

A

5’/3’ - monodeiodinase

41
Q

What deiodinase removes iodide atoms from the inner ring?

A

5/3-monodeiodinase

42
Q

What structure is T3 and T4 based off of?

A

Thyronine (without iodine and sulphate groups)

43
Q

Adding sulphate groups to thyronine allows for what?

A

Makes them more aqueous and so allows them to be excreted by kidney

44
Q

What does T3 and T4 bind to?

A

TBG (Thyroxin-binding globulin)

45
Q

What percentage of T3 and T4 is bound to Thyroxin-binding globulin (TBG)?

A 
T3 = 99.5%
T4 = 99.98%
46
Q

What makes cells sensitive to Thyroid hormones?

A
  • Transporter molecules (carrier mediated)

- 3’/5’ Monodeiodinase

47
Q

WHat does 3’/5’ monodeiodinase do?

A

Converts T4 to T3 (makes it 5 - 10 x more active)

48
Q

What do the thyroid hormones bind to inside the nucleus?

A

Thyroid hormone receptor (transcription factor)

- Binds to thyroid response elements

49
Q

What does the thyroid hormone receptor act as a heterodimer alongisde?

A

Retinoid X receptor (RXR)

50
Q

What vitamin binds to retinoid X receptor?

A

Vitamin A

51
Q

What is activated when thyroid hormone binds to the Thyroid hormone receptor?

A

Thyroid response element - DNA starts to unwind which revelas the codon sequence which is transcribed

52
Q

What proteins do Thyroid hormones stimulate to be produced?

A
  • Na+/K+ATPase
  • Gluconeogenic enzymes
  • Respiratory enzymes
  • Myosin heavy chains
  • Beta adrenergic receptors
53
Q

What is Basal Metabolic Rate (BMR)?

A

How quickly one uses oxygen to make ATP inside cells

54
Q

By how much can hyperthyroidism increase the BMR by?

A

Up to 100%

55
Q

By how much can hypothyroidism decrease the BMR by?

A

50 - 60%

56
Q

What are the physiological actions of the thyroid hormones (e.g on carbohydrate, fat and protein stores)?

A
  • 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
Q

How do goitrogens cause hypothyroidism?

A

Excess iodine, thiocyanate or pechlorate cause excess TSH secretion and hypertrophy of thyroid and hyothyroidism

58
Q

How does Graves disease cause hyperthyroidism?

A

Long-acting thyroid stimulator (LATS - autoimmune stimulation of thyroid) - hypertrophy of thyroid and hyperthyroidism

59
Q

How does Hashimoto’s disease cause thyroid disorders?

A
  • Autoimmune destruction of thyroid
  • Antibodies block TSH receptor and destroy follicular cells
  • Atrophy of thyroid and hypothyroidism
60
Q

What is goitre?

A

An enlarged thyroid gland - can be hyper or hypothyroidism

61
Q

What is responsible for exopthalmus?

A

High levels of antibody (not T3 or T4)

- Deposition of mucopolysaccharide behind eye frombinding to TSH receptor on fibroblasts

62
Q

What is severe hypothyroidism known as?

A

Myxedema

MD4001 Physiology (22 decks)

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