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Y3 Patient sem 1 > The thyroid gland and thyroid hormones > Flashcards

The thyroid gland and thyroid hormones Flashcards

1
Q

What do thyroid follicular cells secrete?

A

T3 and T4

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2
Q

What is each thyroid follicule filled with?

A

thyroglobulin - acts as a store for iodide (critical for function of thyroid gland as it contributes to the making of thyroid hormones)

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3
Q

What does the thyroid gland produce?

A

Thyroid hormone as an interaction between thyroid follicular cells and the colloid that sits inside the lumen

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4
Q

What cells sit inbetween the follicles?

A

Parafollicular C cells

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5
Q

What do Parafollicular C cells secrete?

A

Calcitonin (involved in calcium homeostasis)

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6
Q

What is the effect of low T3 on pituitary thyrotropes?

A

To increase the amount of TSH secreted - want to increase amount of thyroid hormone produces
–> this causes thyroid enlargement and increased activity

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7
Q

What is the effect of high T3 on pituitary thyrotropes?

A

We don’t want any more T3, so TRH would be low, and T3 would cause thyrotropes to reduce amount of TSH being secreted.
–> reduced activity in thyroid gland and reduced hormone will DECREASE thyroid gland

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8
Q

What receptors do thyroid follicular cells contain?

A

Receptors for TSH

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9
Q

What is the TSH receptor?

A

A G-protein-coupled receptor which activates adenylate cyclase to produce the intracellular messenger cAMP

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10
Q

What does cAMP do?

A

Activates all functional aspects of the thyroid cell, including:
o thyroglobulin synthesis (colloid in center)
o iodide pumping
o iodination by thyroid peroxidase
o endocytosis, proteolysis and hormone release

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11
Q

What transporters are in the basolateral membrane of follicular cells?

A
  • Sodium/Iodide Symporter (NIS)

- Na+/K+ ATPase

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12
Q

What does the Sodium/Iodide Symporter (NIS) do on the basolateral side of follicular cells?

A

brings iodide ions INTO thyroid follicular cells

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13
Q

What does the Na+/K+ ATPase pump do?

A

energy using process that co-transports sodium (OUT) and potassium (IN), gradient is needed to maintain

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14
Q

What is the pendrin transporter?

A

Sits on apical cell membrane of follicular cells and transports iodide ions INTO follicle

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15
Q

What is thyroglobulin?

A
  • Thyroglobulin – produced in the thyroid follicular cells, through Endoplasmic reticulum, then released via exocytosis into thyroid lumen
  • Needed as well as iodide for thyroid hormones
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16
Q

What is TPO?

A
  • Thyroid peroxidase enzyme complex
  • spans the apical membrane
  • responsible for iodination of Thyroglobulin (tg)
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17
Q

What does the Thyroglobulin backbone contain?

A

Many tyrosine residues and the TPO adds iodines onto these molecules (can add in 2 different places)

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18
Q

What do the 2 different places on the Tg backbone for iodination lead to?

A
  • If 2 of the residues are iodinated, its known as Di-iodotyrosine (DIT)
  • If only 1 of the molecules is iodinated, its known as Mono-iodotyrosine (MIT)
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19
Q

What is produced if you conjugate 2 DIT molecules?

A

T4

20
Q

What is produced if you conjugate a DIT with a MIT?

A

T3

21
Q

What happens to iodotyrosines on the Tg backbone?

A

Taken back into the cell by endocytosis. Once its taken back into the cell, it will be subject to proteolysis via the lysosome and this will release the T4 and T3.
(any excess Tg and Iodine can be recycled)

22
Q

What is reverse T3?

A

Inactive compound formed when MIT is in a different position - small amount produced and secreted (1%)

23
Q

Is T4 hydrophobic or hydrophillic?

A

HYDROPHOBIC

  • insoluble in serum
  • Therefore, transported in serum in conjunction with specific binding proteins
  • Binding proteins synthesised in liver
  • Liver disease can lead to loss of effective T4 transport (due to reduce synthesis of binding proteins) to peripheral tissues
24
Q

What are thyroid binding proteins?

A 
• Thyroxine-binding globulin (TBG)
     o	Binds 70-75% of plasma T4 
     o	Larger circulating reservoir of T4
     o	Prevents loss in urine (because its bound)
• Transthyretin (TTR)
     o	Binds 20% of plasma T4
     o	Important for delivery to CNS
• Albumin 
     o	Binds 5-10% of plasma T4
25
Q

What can TBG bind?

A

T4 and T3; half life of 5 days

26
Q

What can TTR bind?

A

ONLY T4; half life 2-3 days

27
Q

What can Albumin bind?

A

T3 (30%) and T4 (10%)

28
Q

Can bound T3 and T4 enter cells?

A

NO

29
Q

How do T3 and T4 enter cells?

A

Free T3 and T4 can enter cells via specific transporters (e.g. MCT8, MCT10, OATP1c1)

30
Q

Which out of T3 and T4 is more active?

A

T3 is biologically active, T4 is inactive and must be converted to T3 by intracellular iodothyronine deiodinases (DIO) inside cells (REMOVE IODINE)

31
Q

What are Iodothyronine deiodinases ?

A
  • Seleno-cysteine containing enzymes

* Selenium accepts iodide

32
Q

What Iodothyronine deiodinases convert T4 into T3?

A

DIO1 and DIO2

33
Q

What would DIO1 and DIO3 do to T4?

A

Create reverse T3 (removes the wrong iodine)

34
Q

Where is DIO1 found and what does it do?

A

o Predominates in liver, kidney and muscle (tissues with highest blood supply)
o Also found in thyroid
o Produces most of the circulating T3 (OUTSIDE OF CELL) – in tissues with high blood supply so can be TRANSPORTED

35
Q

Where is DIO2 found and what does it do?

A

o Predominates in areas of CNS, pituitary thyrotropes
o Controls intracellular T3 concentration
o Important for feedback regulation
o Found in skeletal muscle in some species

36
Q

What does DIO3 do?

A

o Produces inactive rT3
o Prevents thyroid hormone access to specific tissues e.g. during pregnancy
o If you have too much thyroid hormone, you could have an increase in DIO3 in order to protect tissues from thyroid hormone overload

37
Q

Where do thyroid hormones act?

A
  • At thyroid hormone receptors (TR)
  • TRalpha and TRbeta (THRA and THRB)
  • Found in nucleus
  • Form heterodimer with retinoid X receptor (RXR)
  • Functions as transcription factor
  • Binds to TRE
  • 15-fold increased affinity for T3 than T4
  • Increased gene transcription
  • Can also inhibit gene transcription
38
Q

What happens in the anterior pituitary gland ?

A
  • T3-responsive genes include those encoding
  • Increase in growth hormone
  • Decrease amount of prolactin
  • Decreased alpha and beta subunits of TSH
39
Q

Where do T3 and T4 bind?

A

To nuclear hormone receptors to alter gene transcription in target cells

40
Q

What are the biological actions of thyroid hormones?

A
  1. Control of metabolic rate
  2. Growth
  3. Foetal development
  4. Cardiovascular effects
  5. Musculoskeletal effects
41
Q

How do thyroid hormones control basal metabolic rate?

A
  • To increase metabolic rate, we need to increase Na+,K+-ATPase, Mitochondria respiratory enzymes and other enzymes and proteins
  • If you’re going to increase respiratory metabolic enzymes, then you’re going to have an increased oxygen consumption – need to have effect on heart to pump more blood to circulate enzymes
  • Also effect on ventilation in order to increase collection of oxygen
42
Q

What growth-regulating roles do thyroid hormones have?

A
  • Most bodily functions affected
  • Often synergise with other hormones (e.g. with growth hormone in early growth and development)
  • Deficiencies lead to abnormal growth, development, reproduction, behaviour, metabolism
  • Exert effects on all organs and tissues throughout life
43
Q

What roles do thyroid hormones have in foetal development?

A
  • Key role in developing neural and skeletal systems
  • Loss of T4 supply to foetus leads to irreversible mental impairment and dwarfism – known as congenital iodine deficiency syndrome
44
Q

What cardiovascular effects do thyroid hormones have?

A

• In order to increase metabolic rate, you need an increased cardiac output
• T3 increases:
o Cardiac contraction and output
o Heart rate
o Oxygen supply to tissues
o CO2 removal from tissues
• Direct effects:
o Increased myocardial Ca2+ uptake
o Increased expression of alpha-myosin heavy chain (help with contraction) and decreased beta
o Increased expression of RYR in SR
• Indirect effects:
o Increased metabolism, thermogenesis and vasodilation
o Increased sensitivity to catecholamines

45
Q

What musculoskeletal effects do thyroid hormones have?

A
  • T3 has a potent stimulatory effect on bone turnover, increasing both formation and resorption
  • T3 increases linear bone growth after birth
  • T3 increases rate of muscle relaxation
  • Normal skeletal muscle function requires T3

Y3 Patient sem 1 (22 decks)

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