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Endocrine Exam 1 > 5 - Thyroid Hormones > Flashcards

5 - Thyroid Hormones Flashcards

1
Q

What is the functional unit of the thyroid gland?

A

Follicles

  • Follicular cells are arranged around a central cavity (lumen)
  • This lumen contains colloid, which is a protein-rich fluid
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2
Q

What are parafollicular cells?

A

The cells that surround the follicles

- These cells produce calcitonin

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3
Q

What is the main source of iodine?

A

The diet

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4
Q

How is iodine accumulated by the thyroid follicular cells?

***Objective

A
  • Iodide is concentrated by follicular cells in an energy-dependent manner.
  • The energy of the sodium electrochemical gradient across the cell membrane powers uptake of iodide.
  • The iodide ions exit the follicular cell and enter the lumen of the follicle via an iodide channel located in the apical membrane.
  • This is a passive process, with iodide ions flowing down their concentration gradient.
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5
Q

What is thyroglobulin?

A
  • Thyroid hormones are derived from thyroglobulin, a large, homodimeric glycoprotein
  • Thyroglobulin is made by the follicular cells and secreted through the apical membrane into the lumen of the follicles, where it forms the major component of colloid
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6
Q

What is meant by organification of iodine?

A

Incorporation of iodine into thyroglobulin is referred to as the organification of iodine

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7
Q

Why is iodine needed?

A

Iodinated thyroglobulin molecules are coupled together to form T3 and T4 - thyroid hormones

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8
Q

What enzyme is responsible for the organification of iodine?

A

Thyroid peroxidase

Thyroid peroxidase is a

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9
Q

What does this enzyme (thyroid peroxidase) require for activity?

*** Objective

A
  • Iodide ions (a reducing agent aka electron donor)
  • Hydrogen peroxide

Iodide ions reduce hydrogen peroxide to water

The hydrogen peroxide comes from calcium-dependent NADPH oxidases, which are located near thyroid peroxidase

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10
Q

What happens to the oxidized iodine?

A

I- is oxidized to I (atomic iodine)

- Iodine reacts with tyrosine residues found within a thyroglobulin molecule

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11
Q

What forms from iodine and tyrosine found within thyroglobulin?

A

Monoiodothyronine (MIT)

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12
Q

What does MIT react with?

A

MIT can react with another iodine to form diiodothyronine (DIT)

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13
Q

In terms of thyroid hormone synthesis, what is meant by ‘coupling’?

*** Objective

A

Thyroid peroxidase enzyme functions to couple MIT with DIT or couple DIT with another DIT

These form T3 (MIT/DIT) or T4 (DIT/DIT)

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14
Q

Does the thyroid gland have the capacity to store hormone?

*** Objective

A

Yes

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15
Q

How does the thyroid gland store hormone?

*** Objective

A

There is a lot of iodinated thyroglobulin in colloid, meaning that the thyroid can just keep it there and store it

There is a 2 – 3 months supply of thyroid hormone in a normal, healthy individual

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16
Q

What does the release of T3 and T4 require?

*** Objective

A

Proteolysis of thyroglobulin

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17
Q

Describe the process of T3 and T4 release

*** Objective

A
  • Thyroglobulin (big molecule which tyrosin is on) is taken back up into the follicular cells by an endocytic process
  • The endocytic vesicles take the thyroglobulin to the lysosome
  • A process of proteolysis releases T3, T4, MIT, DIT, peptides and free amino acids
  • T3 and T4 are then trafficked out of the cell
  • MIT and DIT are de-ioninated in order to conserve iodine for re-use
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18
Q

Which is more abundant, T3 or T4?

*** Objective

A

T4

More T4 is formed than T3
Typical ratio is 5-7 T4 for every T3

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19
Q

Which is the more biologically active hormone, T3 or T4?

*** Objective

A

T3

Both T3 and T4 are biologically active in their “free” form, but more T3 is free than T4, so it is considered to be more biologically active

20
Q

Where does the conversion of T4 to T3 occur?

*** Objective

A

About 40% of T4 is converted to T3, particularly in the liver and kidneys

21
Q

How does the conversion of T4 to T3 occur?

*** Objective

A

Deiodination

There are three classes of deiodinated enzymes (deiodinases)

22
Q

What process accounts for thyroglobulin found in the serum?

*** Objective

A

Transcytosis

Certain endocytic vesicles are routed from the apical membrane to the basolateral membrane, where they thyroglobulin that they contain is released into the bloodstream by exocytosis

23
Q

What is the clinical significance of thyroglobulin in the serum via transcytosis?

*** Objective

A

Can be a sign of…

  • Thyroiditis
  • Graves disease
  • Thyroid malignancy
24
Q

Describe how thyrotropin releasing hormone (TRH) signals thyroid stimulating hormone (TSH; thyrotropin) release.

*** Objective

A
  • Parvicellular neurons of the hypothalamus release TRH
  • TRH goes to the anterior pituitary via the portal hypophysial system
  • TRH binds to a G-protein receptor
  • Phospholipase C is activated
  • Calcium is released, which triggers exocytosis of vesicles containing TSH (thyroid stimulating hormone; thyrotropin)
25
Q

What are the roles of TSH?

*** Objective

A
  • Triggers a signaling cascade
  • Stimulates all aspects of thyroid hormone synthesis/secretion
  • Stimulates growth of thyroid gland
  • Has multiple effects on thyroid-specific transcription factors
26
Q

How is the TSH signal transduced?

*** Objective

A

Via binding to the TSH G-protein coupled receptor

  • This stimulates a signaling cascade
  • This involves both adenylate cyclase and phospholipase C
27
Q

How are thyroid hormones regulated by feedback? (3 ways)

*** Objective

A
  • TRH is inhibited by high T3 levels
  • TRH receptors are reduced in number by high T3/T4 levels
  • TSH translation and release is reduced by high T3/T4
28
Q

How are thyroid hormones transported in the blood?

*** Objective

A

The majority of T3 and T4 is bound to carrier proteins when circulating in the blood

  • Thyroid-binding globin
  • Transthyretin
  • Albumin
29
Q

Why don’t thyroid hormones freely flow through the blood?

*** Objective

A

This is because they are hydrophobic and it increases the half-life of the hormones to be transported by a carrier protein (by preventing them from being cleared by the kidneys)

30
Q

What do we call thyroid hormones that are not bound to carrier proteins?

A

Biologically active hormones that are in the “free” form

31
Q

What process did we talk about before that converts T4 to T3?

A

Deiodination

32
Q

What are the major sites of deiodination?

A

Liver and kidney

33
Q

What are the three types of deiodination enzymes?

*** Objective

A
  • Type I
  • Type II
  • Type III
34
Q

Describe type I deiodinase enzymes

*** Objective

A

Type I

  • Primary enzyme involved in the production of circulating T3
  • Also a major source of T3 in peripheral tissues
  • Also produces rT3
35
Q

Describe type II deiodinase enzymes

*** Objective

A

Type II

  • Converts T4 to T3
  • Important enzyme in tissues that generate T3 locally from T4 in the circulation, rather than just getting T3 from the circulation
  • This is the case for pituitary and hypothalamic cells
36
Q

Describe type III deiodinase enzymes

*** Objective

A
  • Considered to be the MAJOR physiological terminator of thyroid hormone action in the peripheral tissues
  • Converts T4 to rT3 and T3 to T2, both of which are inactive
  • This means that type II inactivates both T4 and T3
37
Q

What is the importance of sulfation in the metabolism of thyroid hormones?

*** Objective

A

Sulfation increases the solubility of thyroid hormones and may facilitate their removal in bile and/or urine

38
Q

What role does glucuronidation play in thyroid hormone metabolism?

*** Objective

A

Glucuronidation

  • Occurs in the liver
  • Increases the water solubility of thyroid hormones
  • Facilitates elimination in bile
39
Q

How do thyroid hormones stimulate the basal metabolic rate?

*** Objective

A

Receptors for thyroid hormones are found in virtually all tissues, so it has a widespread effect

They increase the basal metabolic rate by increasing the transcription of Na/K- ATPase - this is responsible for most of the increased metabolism

40
Q

What are some other effects that thyroid hormones have on the body other than an increase in metabolism?

*** Objective

A
  • Increased cardiac output
  • Increased carbohydrate metabolism
  • Increased lipid metabolism
  • Increased bone turnover
  • Increased erythropoietin production
  • Increased gut motility
  • Multiple endocrine effects
41
Q

What are the general consequences of HYPERthyroidism?

*** Objective

A
  • excessive heat production
  • nervousness
  • insomnia
  • increased heart rate
  • weight loss
  • increased appetite
42
Q

What is Grave’s disease?

*** Objective

A

An autoimmune disease that is characterized by auto-antibodies which bind to the TSH receptor, making it constituently active

The release of thyroid hormone is therefore done regardless of need

43
Q

What are the general consequences of HYPOthyroidism?

*** Objective

A
  • increased sensitivity to cold
  • decreased basal metabolic rate
  • lethargy
  • weight gain without increased caloric intake
44
Q

What is Hashimoto thyroiditis?

*** Objective

A

An autoimmune disease that is characterized by auto-antibodies for one of several things…

  • Thyroid peroxidase
  • Thyroglobulin
  • TSH receptor-blocking antibodies
  • Other

This leads to decreased production and/or secretion of the thyroid hormones

45
Q

How do the thyroid hormones enter their target cells?

*** Objective

A

Need to know that this does NOT occur by passive diffusion through a lipid bilayer

  • There is a high affinity/low capacity transport system that exists to transport the hormones
  • This is an ACTIVE process that may require energy from the sodium electrochemical gradient
46
Q

Describe in general terms how the thyroid receptor/retinoid X receptor complex regulates transcription in response to thyroid hormone.

*** Objective

A
  • Thyroid hormones work by binding to receptors in the nucleus
  • They often bind to DNA as heterodimers
  • The other component of a dimer is often times RXR or retinoid X receptor
  • Once they bind to receptors, there is a conformational change in the thyroid hormone receptor
  • This leads to relaxation of chromatin and enhancement of transcription

Endocrine Exam 1 (18 decks)

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