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Physiology > Thyroid Hormone > Flashcards

Thyroid Hormone Flashcards

1
Q

What regulates somatic growth and body mass?

A

Genes, nutrition, activity and hormones.

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2
Q

What does growth from the fertilised ovum involve?

A

Hyperplasia

Hypertrophy

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3
Q

Hyperplasia

A

increase in the number of cells

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4
Q

Hypertrophy

A

increase in the size of cells

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5
Q

What does growth depend on?

A

Genetic contribution

Nutrition

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6
Q

What hormones regulate linear growth?

A

GH (growth hormone), IGF-1 and IGF-2 (insulin-like growth factors 1 and 2), insulin, THs, glucocorticoids, androgens and estrogens.
Deficiencies (or excesses) of these affects normal growth and development.

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7
Q

What hormones are the major determinants of growth in normal postuterine life?

A

GH and IGF-1.

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8
Q

What does control of body mass depend on?

A

Many newly discovered factors made in adipose, intestine, hypothalamus, and other tissues that regulate appetite and energy expenditure.

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9
Q

When do changes in linear and body mass occur?

A

Simultaneously.

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10
Q

Where is leptin made?

A

Protein made almost exclusively in adipocytes.

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11
Q

What is the path of leptin?

A

Once secreted into the blood, leptin crosses the BBB (blood-brain barrier) to modulate specific neurons in the arcuate nucleus of the hypothalamus that control feeding behaviour.

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12
Q

What is the relationship between plasma leptin levels and mass of adipose tissue?

A

Directly proportional

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13
Q

What is the function of leptin?

A

Long-term regulator of CNS feeding behaviour.

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14
Q

What is the effect of ghrelin?

A

Promotes appetite – systemically administered ghrelin acutely increases food intake when given at physiological doses.

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15
Q

When and where is ghrelin made?

A

Synthesised by endocrine cells in the gastric mucosa in response to fasting.

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16
Q

Are ghrelin levels high or low in lean individuals?

A

Low

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17
Q

Where does ghrelin act from?

A

Acts via the arcuate nucleus of the hypothalamus.

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18
Q

Are plasma leptin concentrations high or low in overweight/obese individuals?

A

High

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19
Q

What are the names of thyroid hormones?

A

Thyroxine (tetraiodothyronine or T4)

Triiodothyronine (T3)

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20
Q

What are thyroid hormones essential for?

A

Normal development, growth and metabolism.

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21
Q

What type of hormones are TH?

A

Lipophilic (no cell membrane exists)

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22
Q

Where does TH act from?

A

Act via nuclear receptors.

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23
Q

What does TH regulate?

A

Transcription of cell proteins.

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24
Q

What else is located in the thyroid gland?

A

C cells

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25
Q

What are C cells responsible for?

A

Synthesis and secretion of a peptide hormone called Calcitonin.

26
Q

What is calcitonin released in response to and what does it do?

A

Hypercalcaemia
Lowers the plasma concentration of free calcium ions but it is not important in the normal control of calcium ion metabolism.

27
Q

Where is the thyroid gland located?

A

Anterior to the cricoid cartilage.

28
Q

What does the thyroid gland comprise of?

A

Numerous follicles which are hollow, spherical structures filled with a structure called colloid.

29
Q

What is the wall of each spherical follicle made up of?

A

Follicular cells

30
Q

What are follicular cells responsible for?

A

Trapping of iodine.

31
Q

What is the trapping of iodine responsible for?

A

Thyroid hormone synthesis.

32
Q

What do follicular cells secrete and where are the components secreted into?

A

Iodine
Thyroglobulin (major protein of the thyroid colloid)
These are secreted into the lumen of the follicle.

33
Q

What is the first step to synthesis and secretion of T4 and T3?

A

Step 1
Thyroid stimulating hormone (TSH) stimulates the uptake of iodide, from the extracellular fluid, into the follicular cell via a sodium dependent cotransporter.

34
Q

What is the first step of synthesis and secretion of T4 and T3?

A

Step 1
Thyroid stimulating hormone (TSH) stimulates the uptake of iodide, from the extracellular fluid, into the follicular cell via a sodium dependent cotransporter.

35
Q

What is the second step of synthesis and secretion of T4 and T3?

A

Step 2
Iodide exits the cell and enters the lumen of the follicle, most likely via a membrane transport protein called pendrin. Iodide oxidises to iodine as part of this step.
Follicular cell also secretes a protein called thyroglobulin, which includes tyrosine amino acid residues, acts as a peptide scaffold within the colloid for the synthesis of T3 and T4.

36
Q

What is the third step of synthesis and secretion of T4 and T3?

A

Step 3
TSH also stimulates iodinisation of thyroglobulin in the lumen of the follicle. In the colloid, iodine attached to tyrosine residues of thyroglobulin forms monoiodotyrosine (MIT), an attachment of two iodines forms diiodotyrosine (DIT).

37
Q

What is the fourth step of synthesis and secretion of T4 and T3?

A

Step 4
Conjugation of two diiodotyrosine forms T4 and coupling of a mono and a diiodotyrosine will form T3. AT this stage, both T3 and T4 remain linked to the thyroglobulin.

38
Q

What is the fifth and sixth step of synthesis and secretion of T4 and T3?

A

Steps 5 and 6
The TSH stimulates the endocytosis of iodinated thyroglobulin from the colloid back into the follicular cells. This is followed by proteolysis leading to the formation of both T4 and T3. Note on this figure that a deiodinase converts some of the T4 to T3.

39
Q

What is the seventh step of synthesis and secretion of T4 and T3?

A

Step 7

TSH stimulates the secretion of T4 and T3 into the circulation. The mechanism of secretion remains poorly understood.

40
Q

Which step does TSH not stimulate?

A

Step 2

41
Q

What is essential for the synthesis of T4 and T3?

A

Dietary iodine

42
Q

Which type of TH is more active and why?

A

T3

Non-thyroidal tissues (principally the liver and kidneys) metabolise T4 into T3.

43
Q

Which type of TH is secreted more?

A

T4

44
Q

What are ~99% of THs highly bound to in the circulation?

A

Plasma proteins

45
Q

What plasma proteins are THs highly bound to and where are they made?

A

Thyroid-binding globulin (TBG), albumin and transthyretin (TTR).
Made by the liver.

46
Q

What are the roles of the plasma proteins which THs are bound to?

A

Act as a large buffer pool of THs in the circulation.
Helps pro-long the half-lives of both T4 (8 days) and T3 (~24 hours).
Large pool of T4 provides a reserve of prohormone available for synthesis of T3.

47
Q

Why can protein bound hormones be used to replenish the active hormone pool?

A

Any protein bound hormone is in dynamic equilibrium with the free hormone pool so this can be used to replenish that active pool.

48
Q

What are free or unbound hormones responsible for?

A

Actions of THs on their target tissues.

49
Q

What part of a target cell do THs act on?

A

Thyroid hormones are lipophilic so act via intracellular receptors located in the nucleus that will then regulate gene expression.

50
Q

How do T4 and T3 enter target cells?

A

Either by simple diffusion across the plasma membrane or by carrier mediated transport. (this step remains poorly understood)

51
Q

What converts T4 into T3 when T4 is inside the cell?

A

A cytoplasmic monodiodinase.

52
Q

What are the cytoplasmic levels of both T4 and T3?

A

Approximately equal.

53
Q

Where do TH receptors bind to?

A

Nuclear DNA at thyroid response elements in the promotor region of genes that are regulated by thyroid hormones.

54
Q

What does the binding of T3 or T4 to receptor regulate?

A

Transcription of these genes.

55
Q

Which proteins’ gene expression are regulated by TH?

A

Metabolic and respiratory enzymes, the sodium potassium pump, the contractile protein myosin, beta adrenergic receptors and many other proteins.

56
Q

What effect do THs have on basal metabolic rate and what is their mechanism of action?

A

Increases BMR by stimulating both catabolic and anabolic reactions in pathways affecting CHOs, proteins and lipids.

57
Q

What effect do THs have on hepatic gluconeogenic activity and what is their mechanism of action?

A

Increases it by inducing the expression of several key glycogenic enzymes.

58
Q

Do THs have an effect on plasma glucose concentration?

A

Generally do not providing the pancreas responds by increasing insulin secretion.

59
Q

Describe the graph

A

Plot on left hand side shows the effects of both T3 and T4 on oxygen utilisation. Used as an indicator of basal metabolic rate. Shows for the same dose of T3 and T4, it is T3 that gives rise to the biggest increase to BMR.

60
Q

Describe the graph

A

Plot on right hand side illustrates the time delay between dose and peak response. In this experiment, an experimental animal model is fed a single dose of thyroid extract that’ll contain both T3 and T4 on day 0. BMR is measured at regular time intervals thereafter, up to 40+ days. Peak response to that single dose occurs round about day 10 or day 10+. This is because it takes time for the gene expression regulated by the TH to be manifested into measurable changes in protein function i.e. it takes time for gene expression levels to change protein expression levels in those target cells and for the effects of those protein changes to result in a physiological response.

Physiology (2 decks)

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