Thyroid Hormone Physiology Flashcards

1
Q

Thyroid Structure:

A

insert diagram

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2
Q

Thyroid Gland: Overview:

A
  • largest of endocrine glands
  • produces thyroid hormones that regulate
    the basal metabolic rate
  • requires dietary iodine which is absorbed
    as iodide
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3
Q

Recommended daily intake of iodide for adults is

A

150 micrograms

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4
Q

Thyroid Gland: Location:

A
  • inferior to the larynx
  • either side of the cricoid cartilage and
    upper trachea
  • covered by strap muscles of the neck,
    overlapped by sternocleidomastoid
    muscles
  • enclosed by pretracheal fascia, which
    attaches it to the larynx
  • weight = 15-20g
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5
Q

Thyroid Gland Development:

A
  • from the floor of the pharynx
  • near the root of the tongue that descends
    into the neck as a downgrowth
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6
Q

Thyroid Gland: Histology:

A

insert diagrams

colloid is stained pink because rich in protein
found inside epithelial cell

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7
Q

Colloid:

A
  • substance found in thyroid
    follicles
  • rich in thyroglobulin
  • large, dimeric glycoprotein
  • thyroglobulin is produced in
    the ER and Golgi of epithelial
    cells
  • secreted in the follicle colloid
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8
Q

The thyroid gland secretes the metabolic hormones:

A
  • T4 = thyroxine = 93%
  • T3 = triodothyronine = 7%

tyrosine based hormones that have four iodines and three iodine respectively

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9
Q

Calcitonin:

A
  • hormone
  • produced by thyroid C cells
  • involved in calcium homeostasis
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10
Q

Which tyrosine based hormone is a precursor of the other?

A

T4 is a precursor of T3
can be converted to the active form of T3 through the removal of one iodine

removal of iodine catalysed by deiodinase enzymes converting T4 into T3

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11
Q

Where is the majority of T3 produced?

A

peripheral extra-thyroidal tissues
mainly liver and kidney

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12
Q

Deiodinases:

A
  • D1 = liver, kidney, thyroid
  • D2 = muscle, brain, pituitary,
    skin and placenta
  • D3 = converts T4 into
    reverse/inactive T3 ->
    control mechanism
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13
Q

Thyroglobulin synthesis:

A
  • produced in epithelial cells of
    follicles
  • thyroglobulin is glycosylated
    in Golgi
  • secreted to the follicular space
    and is stored as colloid
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14
Q

Synthesis of Thyroid Hormones:

A
  • thyrogobluin is a big molecule
    with tyrosine
  • T3 and T4 are tyrosines with
    iodine
  • in the basolateral membrane
    of epithelial cell
  • Na+/I- symporter transports 2
    Na+ and 1 I- into the cell
  • I- diffuses down the epithelial
    cell and transported into the
    follicular lumen where colloid
    is stored
  • in the colloid I- is oxidised into
    iodine
  • Pendrin (P) is involved in this
    process and is a protein
  • apical membrane engulfs
    blobs of colloid and is taken
    into the cell again
  • colloid droplets fuse with
    lysosome
  • proteolytic enzymes hydrolyse
    colloid into thyroglobulin
  • TPO = thyroid peroxidase
  • catalyses the oxidation of I-
    into iodine and the
    subsequent binding to
    thyrogobulin
  • T3 = 3 iodine molecules
  • T4 = 4 iodine molecules

one tyrosine can take one or two iodine molecules

tyrosines can join together in groups of 2 each with one or two iodines can join

thyroglobulin acts as a store of tyrosine dimers

when T3 and 4 needs to be produced the apical membrane takes in globs of colloid via endocytosis

insert diagram

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15
Q

Advantage of stored colloid:

A

T3 and T4 are hormones that control metabolic rate

important that they are readily available

always some hormone precursor stored for quick secretion

if a cell can not produce thyroglobulin, symptoms will not show for a few months due to the stores of colloid

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16
Q

Thyroglobulin:

A

insert diagram

17
Q

Synthesis of Thyroid Hormones:

A

insert flowchart

18
Q

Na+/I- Symporter:

A
  • basolateral membrane
  • transporters 2 Na+ and 1 I-
    into the epithelial cell
  • energy is provided by the
    sodium gradient generated by
    the Na+/K+ ATPase pump
19
Q

Pendrin assists movement of I- into colloid through apical membrane via

A

pendrin/Cl- antiporter (Cl- enters epithelial cell)

insert diagram

20
Q

Thyroid Hormone Regulation:

A
  • HPA axis (hypothalamus -
    pituitary - thyroid axis)
  • hypothalamus produces
    thyrotropin releasing
    hormone (TRH)
  • binds to the pituitary resulting
    in production of thyrotropin
    (TSH) by the anterior pituitary
    gland cells

TRH activates production of TSH which activates the production of T4 which is subsequently converted to T3

Negative Feedback Loop:

Increased thyroid hormone conc in blood/body fluids/ peripheral tissues inhibits pituitary and hypothalamus production of TRH and TSH

21
Q

TRH:
- synthesis occurs in
- transport to the pituitary?

A
  • hypothalamic neurons
  • via the hypothalamic -
    hypophyseal portal system of
    blood circulation
22
Q

Thyroid Hormone Regulation:

A

insert diagram

23
Q

Thyrotropin (TSH):
- produced by
- involvement
- inhibited by

A
  • thyrotrope cells of the
    anterior pituitary
  • involved in synthesis (gene
    expression regulation role)
    and secretion of T3 and T4
  • T3 and T4 inhibit TSH
    synthesis, glycosylation and
    secretion
24
Q

TSH: Mechanism of Action:

A

insert diagram

TSH binding to receptor which is Gs GCPR

GTP replaces GDP

Adenylate Cyclase activated

increase in conc of cyclic AMP production

TSH receptor binding can also activate phospholipase C

all results in proliferation, hormone synthesis and secretion

insert diagram

25
Q

TSH and Cold Exposure:

A
  • excitation of the hypothalamic
    mechanism that controls
    thermoregulation
  • leads to increased production
    and secretion of TRH
  • living in arctic -> 15-20%
    increased metabolic rate
26
Q

TSH and Fasting:

A
  • prolonged fasting reduces
    leptin levels
  • causing reduced secretion of
    TRH, TSH and thyroid
    hormones
  • results in reduced metabolic
    rate
27
Q

TSH and Emotions:

A
  • anxiety, excitement
  • sympathetic nervous system
    stimulation
  • decrease in TSH secretion
28
Q

Thyroid Hormone Transport:

A
  • T3 and T4 are bound to
    plasma proteins in the blood
  • these plasma proteins are
    synthesised in the liver: TBG,
    TTR, albumin
  • allows slow release to tissues
    and cells
  • T3 is released faster than T4
  • 50% of T4 circulating in the
    blood is released to tissues
    every 6 days
  • 50% of T3 circulating in blood
    is released to tissues in 1 day
  • T3 has lower affinity for
    plasma proteins than T4
29
Q

How do circulating T3 and T4 enter cells?

A
  • active membrane transport
  • MCT8 transporter protein
30
Q

Through which process does thyroid hormones function?

A

Transcription activation

31
Q

Thyroid Hormone Function: Transcription Activation:

A
  • T4 must be converted to T3
    through deiodinase action
  • T3 binds to thyroid hormone
    receptors (TRS), which is has a
    high affinity for
  • TRs form heterodimers with
    Retionoid X Receptors
  • TRs bind on short DNA
    sequences called thyroid
    hormone response elements
    or hormone response
    elements
  • results in regulation of gene
    expression
  • generally initiates synthesis of
    proteins that might change
    cardiac output, tissue blood
    flow and respiration
32
Q

Thyroid Hormone Function:

A
  • transcription activation

insert diagram

33
Q

Action of Thyroid Hormones on Metabolism:

A
  • daily thyroid hormone
    production of T4 is 100
    micrograms and 35
    micrograms of T3
  • more T3 = faster metabolism
  • more T4 = slower metabolism

insert graphs

34
Q

Which thyroid hormone directly influences basal metabolic rate?

A

T3

35
Q

Cellular Response to Thyroid Hormone Activity:

A
  • increase in number of
    mitochondria
  • increased Na=/K+ ATPase
    pump activity resulting in
    increased ion transport and
    cellular energy consumption
  • quick glucose uptake and
    increased
    glycolysis/gluconeogenesis
    rate
  • increased insulin secretion
  • decreased plasma cholesterol
  • increased enzyme synthesis
    and vitamin uptake
  • increased respiration due to
    increase of metabolic rate
36
Q

Body function response to thyroid hormone activity:

A
  • organogenesis, growth,
    development
  • bone turnover
  • energy expenditure
  • metabolism
  • erythropoiesis
  • HR, blood flow, CO
  • muscle contraction and
    relaxation
  • endocrine gland activity
  • neural activity
37
Q

How does T5 regulate gene expression?

A
  • via transcription activation, in
    which it binds to hormone
    receptors on DNA hormone
    response elements