Thyroid Hormone Physiology Flashcards
Thyroid Structure:
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Thyroid Gland: Overview:
- largest of endocrine glands
- produces thyroid hormones that regulate
the basal metabolic rate - requires dietary iodine which is absorbed
as iodide
Recommended daily intake of iodide for adults is
150 micrograms
Thyroid Gland: Location:
- 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
Thyroid Gland Development:
- from the floor of the pharynx
- near the root of the tongue that descends
into the neck as a downgrowth
Thyroid Gland: Histology:
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colloid is stained pink because rich in protein
found inside epithelial cell
Colloid:
- 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
The thyroid gland secretes the metabolic hormones:
- T4 = thyroxine = 93%
- T3 = triodothyronine = 7%
tyrosine based hormones that have four iodines and three iodine respectively
Calcitonin:
- hormone
- produced by thyroid C cells
- involved in calcium homeostasis
Which tyrosine based hormone is a precursor of the other?
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
Where is the majority of T3 produced?
peripheral extra-thyroidal tissues
mainly liver and kidney
Deiodinases:
- D1 = liver, kidney, thyroid
- D2 = muscle, brain, pituitary,
skin and placenta - D3 = converts T4 into
reverse/inactive T3 ->
control mechanism
Thyroglobulin synthesis:
- produced in epithelial cells of
follicles - thyroglobulin is glycosylated
in Golgi - secreted to the follicular space
and is stored as colloid
Synthesis of Thyroid Hormones:
- 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
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Advantage of stored colloid:
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
Thyroglobulin:
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Synthesis of Thyroid Hormones:
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Na+/I- Symporter:
- 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
Pendrin assists movement of I- into colloid through apical membrane via
pendrin/Cl- antiporter (Cl- enters epithelial cell)
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Thyroid Hormone Regulation:
- 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
TRH:
- synthesis occurs in
- transport to the pituitary?
- hypothalamic neurons
- via the hypothalamic -
hypophyseal portal system of
blood circulation
Thyroid Hormone Regulation:
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Thyrotropin (TSH):
- produced by
- involvement
- inhibited by
- 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
TSH: Mechanism of Action:
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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
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TSH and Cold Exposure:
- excitation of the hypothalamic
mechanism that controls
thermoregulation - leads to increased production
and secretion of TRH - living in arctic -> 15-20%
increased metabolic rate
TSH and Fasting:
- prolonged fasting reduces
leptin levels - causing reduced secretion of
TRH, TSH and thyroid
hormones - results in reduced metabolic
rate
TSH and Emotions:
- anxiety, excitement
- sympathetic nervous system
stimulation - decrease in TSH secretion
Thyroid Hormone Transport:
- 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
How do circulating T3 and T4 enter cells?
- active membrane transport
- MCT8 transporter protein
Through which process does thyroid hormones function?
Transcription activation
Thyroid Hormone Function: Transcription Activation:
- 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
Thyroid Hormone Function:
- transcription activation
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Action of Thyroid Hormones on Metabolism:
- daily thyroid hormone
production of T4 is 100
micrograms and 35
micrograms of T3 - more T3 = faster metabolism
- more T4 = slower metabolism
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Which thyroid hormone directly influences basal metabolic rate?
T3
Cellular Response to Thyroid Hormone Activity:
- 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
Body function response to thyroid hormone activity:
- organogenesis, growth,
development - bone turnover
- energy expenditure
- metabolism
- erythropoiesis
- HR, blood flow, CO
- muscle contraction and
relaxation - endocrine gland activity
- neural activity
How does T5 regulate gene expression?
- via transcription activation, in
which it binds to hormone
receptors on DNA hormone
response elements
