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Renal and Endocrine Biology > REB 5. Thyroid Hormone: Synthesis, Transport and Cellular Mechanisms > Flashcards

REB 5. Thyroid Hormone: Synthesis, Transport and Cellular Mechanisms Flashcards

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1
Q

When does the thyroid gland first start to develop in the body?

A

24th day of gestation

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2
Q

Where does the thyroid gland originate from?

A

it originates as proliferation of endodermal epithelial cells on median surface of developing pharyngeal floor

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3
Q

Which pharyngeal arch does the thyroid gland arise from?

A

1st pharyngeal arch

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4
Q

Which duct does the thyroid precursor develop from?

A

thyroid precursor develops from the Thyroglossal Duct, a diverticulum

the thyroid precursor descends in the neck as an initially hollow structure which later solidifies and become bilobed connected by an isthmus

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5
Q

After initial descent, the thyroid gland is still connected to the tongue by the thyroglossal duct, when is the thyroglossal duct fully obliterated?

A

7 to 10 weeks

*note: remnant of duct may persist

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6
Q

After the thyroid gland descends, it forms its mature shape by which week?

A

7 to 8 weeks of gestation

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7
Q

What is the final position of the thyroid gland?

A

anterior to trachea

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8
Q

What is Thyroid Dysgenesis?

A

it is disorders of the thyroid gland development

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9
Q

What are disorders of the thyroid gland development called?

A

Thyroid Dysgenesis

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10
Q

What are the 2 main categories of disorders of the thyroid gland development (Thyroid Dysgenesis)?

A

[1] Ectopic Thyroid Gland

(a) Failure to Descend
(b) Incomplete Descent

[2] Thyroglossal Duct Cyst

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11
Q

What is an ectopic thyroid gland and what are the 2 ways it can occur?

A

Ectopic Thyroid Gland: thyroid tissue is not located in its usual position and it is associated with congenital hypothyroidism (screened for at birth)

Causes:

(a) Failure to Descend - a lingual thyroid, is the most common at base of tongue
(b) Incomplete Descent - if duct does not atrophy, remnant manifests clinically as thyroglossal duct cyst
- 50% present as midline cystic masses just below level of hyoid bone

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12
Q

What are the 2 main associated endocrine glands or cells with the thyroid gland?

A

[1] Parathyroid Glands
[2] Parafollicular or C-Cells

*note: they are both involved with altering calcium levels

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13
Q

Where are the parathyroid glands located and what do they synthesize and secrete?

A
  • they are 2 pairs of small glands on the posterior surface of thyroid gland
  • synthesize and secrete Parathyroid Hormone (PTH)
  • PTH increases blood calcium levels
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14
Q

What is the function of Parathyroid Hormone?

A

it increases blood calcium levels

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15
Q

Where are the parafollicular cells/C cells located and what do they synthesize and secrete?

A
  • they are single cells in epithelial lining of follicle or in groups of connective tissue between follicles
  • they secrete Calcitonin
  • Calcitonin lowers blood calcium levels
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16
Q

What is the function of Calcitonin?

A

it lowers blood calcium levels

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17
Q

The thyroid gland is divided into… or…

A

Clusters or Follicles by connective tissue

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18
Q

What does a follicle in the thyroid gland consist of?

A
  • thin layer of epithelial cells, responsible for synthesis of thyroid hormones
  • colloid, proteinaceous material, thyroglobulin source
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19
Q

Where are the thyroid hormones synthesized?

A

thyroid hormones are epithelial cells and secreted into the lumen of follicle

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20
Q

What is required in the synthesis of thyroid hormones?

A

[1] Thyroglobulin (Protein)
[2] Iodine

note: thyroid hormones are the only constituents in the body that contain bound iodine

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21
Q

What are the 2 types of thyroid hormones?

A

[1] Triiodothyronine (T3) - 3 iodines present

[2] Thyroxine (T4) - 4 iodines present

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22
Q

What is thyroglobulin? What stimulates the synthesis of thyroglobulin?

A
  • it is a precursor for thyroid hormone
  • it is a large dimeric glycoprotein
  • Thyroid Stimulating Hormone (TSH) stimulates the synthesis of thyroglobulin
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23
Q

Where is thyroglobulin synthesized?

A

epithelial cells surrounding the follicle

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24
Q

What is the process in which thyroglobulin is synthesized to thyroid hormone?

A

[1] thyroglobulin synthesis is stimulated by TSH
[2] thyroglobulin synthesized in epithelial surrounding the follicle
[3] thyroglobulin is released into the colloid space
[4] the tyrosine residues of the thyroglobulin are iodinated
- 8 to 10 of the tyrosines are processed into active hormone (out of around 40)

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25
Q

How to form T3 and T4? What is an important enzyme involved with the formation of T3 and T4?

A

[1] DIT + MIT = T3
[2] DIT + DIT = T4

enzyme: thyroperoxidase

26
Q

What is thyroperoxidase? And what are the 2 reactions it is involved in?

A

Thyroperoxidase is an enzyme located on the apical (colloid-facing) membrane of epithelial cells.

It catalyzes 2 reactions:
[1] Iodination of Tyrosines (on thyroglobulin)
- adding iodines
[2] Coupling Reaction (synthesis of thyroxine or triiodothyronine from 2 iodotyrosinne molecules)
- creating T3 and T4

27
Q

How does thyroid hormones move around in the blood? (aka how is it transported?)

A

[1] <1% of T3 and T4 remains unbound or free (hydrophobic hormones)

[2] 99% of T3 and T4 is bound to specialized transport proteins:

(a) Thyroxine-Binding Globulins (TBGs)
(b) Albumin
(c) Other Plasma Proteins

*note: this complex prevents their free diffusion into bodt cells and from excretion

28
Q

What are the 3 types of transport proteins that thyroid hormones may bind to?

A

[1] Thyroxine-Binding Globulins (TBGs)
[2] Albumin
[3] Other Plasma Proteins

29
Q

What are the half-lives of T4 and T3?

A 
T3 = ~1.5 days
T4 = ~6.5 days
30
Q

What thyroid hormone does the thyroid gland secrete the most?

A

It secretes 90% of T4

31
Q

Which thyroid hormone is more biologically active than the other?

A

T3 is more active than T4

32
Q

What can T4 be metabolised to? [2]

A

[1] to biologically active T3

[2] to the biologically inactive, reverse T3

33
Q

What is the average amount of iodine in the adult body? Where is most of the iodine located?

A
  • between 20 and 50 mg of iodine

- more than 60% of iodine is located in thyroid gland

34
Q

the iodine content of food and water is dependent on what?

A
  • dependent on iodine in the soil

- glaciated, mountainous or heavy rainfall areas low in iodine

35
Q

What are some sources of iodine?

A
  • iodized salt
  • seaweed
  • dairy
  • eggs
  • tuna
36
Q

What are goitrogenous substances and what is an example?

A

Goitrogenous Substances - are substances that disrupt the production of thyroid hormones by interfering with iodine uptake in the thyroid gland
- example: cruciferous vefetables and legumes

37
Q

What are the 2 mechanisms of iodine metabolism that can happen?

A

[1] Iodide Excreted by Kidneys

[2] Iodine Taken Up by Thyroid Gland

38
Q

Explain the steps in how iodine is excreted by the kidneys.

A

[1] dietary iodine is absorbed in the GI tract
[2] iodine is converted to iodide in the gut, absorbed + circulated bound to serum proteins
[3] iodide is excreted by the kidneys

39
Q

Explain the steps in how iodine is taken up by the thyroid gland.

A

[1] dietary iodine is absorbed in the GI tract

[2] iodine is converted to iodide in the gut, absorbed + circulated bound to serum proteins

[3] iodide taken up by thyroid gland

[4] transport of iodide into follicular cells depends on the Na+/I- cotransporter

[5] iodide taken up by the thyroid gland oxidized by peroxide in the lumen of the follicleto produce iodine

[6] iodine can then be used to create T3 and T4

40
Q

Explain the basis of the Sodium-Iodide Symporter (NIS)

A

[1] 2 Na+ and 1 I- ion from ECF enter the thyroid epithelial cells

[2] Na+ is then pumped out of the cells by Na+/K+ ATPase pump to maintain high extracellular Na+

*TSH increases activity of iodine transport and Na+/K+ ATPase

41
Q

Hormone synthesis (of TSH) is dependent on…

A

[1] availability of iodide

[2] integrity of thyroid gland

42
Q

Where is Thyrotropin-Releasing Hormone (TRH) synthesized, what is its action and what are some regulators of it?

A

Synthesis:
TRH is synthesized in the hypothalamus and derived from the larger prepro-molecule

Action:
stimulates TSH synthesis in thyrotropes of the anterior pituitary gland

Regulators of TRH Synthesis:

(a) intracellular T3
(b) circulating T4 levels
- inhibits synthesis of TRH
- blocks capacity of TRH to stimulate release of TSH

43
Q

Where is Thyroid Stimulating Hormone (TSH) synthesized and how is it regulated?

A

it is produced by thyrotrope cells in the anterior pituitary gland

Regulated:
[1] suppressed by T3 (mainly beta subunit) in thyrotropes
[2] increased by TRH from hypothalamus

44
Q

What is special about thyroid stimulating hormone (TSH) secretion?

A
  • secreted in low amplitude pulses

- it is lower during day with slightly higher levels at night (circadian)

45
Q

What is Thyroxine Binding Globulin (TBG) and where is it synthesized?

A

it is a glycoprotein synthesized in the liver

46
Q

What is the affinity and capacity of Thyroxine Binding Globulin (TBG)? What does it bind more, T3 or T4?

A
  • it has a high affinity for thyroid hormone
  • low capacity (amount it can hold)
  • mainly carries T4
47
Q

What is the affinity and capacity of Thyroxine Binding Pre-Albumin (TBPA)/Transthyretin? What does it bind more, T3 or T4?

A
  • it has a low affinity for thyroid hormone
  • higher capacity
  • mainly carries T3
48
Q

What is the affinity and capacity of Albumin (ALB)? What does it bind more, T3 or T4?

A
  • it has a low affinity for thyroid hormone
  • it has a high capacity
  • mainly carries T3
49
Q

Is protein-bound thyroid hormone biologically active?

A

No, the thyroid hormone needs to dissociate from the protein to be active

50
Q

Explain the genomic action of thyroid hormones?

A

[1] thyroid hormone receptors are nuclear receptors activated by binding of thyroid hormone

[2] lipophilic T3 binds to nuclear thyroid receptor (TR)

[3] complex binds to thyroid hormone response element (TRE) with Retinoid X Receptor (RXR) [a transcription factor]

[4] TR/DNA/coactivator complex recruits RNA polymerase that transcribes DNA

51
Q

What are some actions of the thyroid hormone?

A

[1] influence body’s basal metabolic rate

[2] initiate the transcription of genes involved in glucose oxidation

[3] thyroid hormones are also required for protein synthesis

[4] development of the nervous system both in utero and in early childhood

[5] thyroid hormones increase the body’s sensitivity to catecholamines

[6] regulate heart rate and increases blood pressure

52
Q

What is the clinical presentation of hyperthyroidism?

A
  • CNS symptoms (nervousness, irritability, fatigue)
  • heat intolerance, elevated metabolic rate, weight loss
  • tachycardia: may develop congestive heart failure
  • hypertension
  • goitre
  • muscle wasting
  • proptosis (apparent bulding of eyes)
53
Q

What is proptosis? What is it a clinical presentation of?

A
  • it is the apparent bulging of the eyes

- it is a clinical presentation of hyperthyroidism

54
Q

What does an early onset of hypothyroidism result in?

A
  • it leads to a delayed or incomplete physical and mental development
  • this is screened for is newborns with the heel prick test
55
Q

What is another name for the adult onset of hypothyroidism?

A

Myxoedema

56
Q

What are the symptoms of the adult onset of hypothyroidism?

A
  • tiredness, lethargy, decreased metabolic rate
  • slowing of mental function and motor activity
  • cold intolerance
  • weight gain
  • goitre
  • hair loss, dry skin
  • may result in coma
57
Q

What does thyroid hormone have on the metabolic rate?

A

[1] Low Thyroid Hormone Levels = Low Metabolic Rate

  • increased protein synthesis (growth)
  • increase glycogen synthesis (storage of energy)
  • anabolic phase

[2] High Thyroid Hormone Levels = High Metabolic Rate

  • increased protein degradation (energy)
  • increased glycogen breakdown (glucose production)
  • catabolic
58
Q

List some of the effects of thyroid hormones on intermediary metabolism.

A
  • increase glucose absorption from GI tract
  • increase carb, lipid and protein turnover
  • increased glycolysis
  • increased glycogenolysis
  • increased gluconeogenesis
  • stimulate fat mobilization and lead to increased free fatty acid
  • increases mitochondrial oxidative phosphorylation (ATP production)

overall result: increased metabolic rate + increased heat/energy production (calorigenic effect)

59
Q

List some of the effects of thyroid hormones on the cardiovascular and respiratory system.

A

cardiovascular system:

  • increase heart rate
  • increase force of cardiac contractions
  • increase stroke volume
  • upregulate catecholamine receptors

respiratory system:
- increase resting respiratory rate

60
Q

List some of the effects of thyroid hormones on growth and tissue development.

A
  • required for GH and prolactin production and secretion
  • required for GH action (growth, cell proliferation)
  • increased growth and maturation of bone
  • increased tooth development and eruption
  • increase growth and maturation of epidermis, hair follicles and nails
  • increase rate and force of skeletal muscle contraction
61
Q

List some of the effects of thyroid hormones on the nervous system.

A
  • essential for normal CNS development
  • increased speed and amplitude of peripheral nerve reflexes
  • enhances alertness
  • enhances memory and learning capacity
62
Q

List some of the effects of thyroid hormones on the reproductive system.

A
  • normal reproductive behaviour and physiology is dependent on normal levels of thyroid hormone
  • follicular development and ovulation
  • maintenance of pregnancy
  • normal spermatogenesis
  • hypothyroidism in particular is commonly associated with infertility

Renal and Endocrine Biology (25 decks)

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