Thyroid Gland Physiology Flashcards
hypothalamus secretes
thyrotropin releasing hormone
thyrotropin releasing hormone stimulates
the anterior pituitary
the anteriorly pituitary secretes
thyroid stimulating hormone
thyroid stimulating hormone stimulates
the thyroid gland
the thyroid gland secretes
triiodothyronine (T3) and levothyroxine (T4) and calcitonin
thyroid gland is made up of
follicles
the follicle is made up of
follicular cells which enclose a central colloid
the colloid consists of
spheres filled with thyroglobulin
surrounding the follicles
are parafollicular c cells which secrete calcitonin
iodide (I-) is
actively transported through the follicular cells through the iodine transporter and into the colloid
iodide in the colloid is then converted
to iodine (I2) using the enzyme thyroid peroxidase
the thyroglobulin within the colloid contains
tyrosine amino acid residues, thyroid peroxidase enzyme then adds I2 onto the tyrosine amino acid residues
this generated either a
singly or doubly iodinated species of tyrosine
if one iodine is added you get
MIT (monoiodotyrosine)
if two iodines are added you get
DIT (diiodotyrosine)
thyroid peroxidase then
combines MIT and DIT through a process called coupling to generate T3 or T4
T3 is made up of a combination of
one MIT and one DIT residue
T4 is made up of a combination
of two DIT residues
why is 90% of the thyroid hormones produced T4 and only 10% T3
because thyroid peroxidase enzyme is much more efficient at combining two DIT residues than a MIT and DIT residue
The T3 and T4 produced in colloid
is bound to the thyroglobulin and stored in the follicular cells via pinocytosis so when TSH acts on the thyroid they can be released into the circulation (by cleavage form thyroglobulin)
T3 is the
major biologically active hormone and is 4x more potent than T4 (thyroxine)
T3 and T4 hormones in the circulation are
hydrophobic and lipohilic so they travel in the blood bound to plasma proteins
plasma proteins for T3 and T4
- 70% of thyroid hormones are bound to thyroxine binding globulin (TBG)
- 20% of thyroid hormones are bound to transthyterin (TTR)
- 5% is bound to albumin
unbound T3 and T4
are the only biologically active thyroid hormones and are known as free T3 and free T4
bound T3 and T4
are biologically inactive
bound T3 and T4 then reach
there target cells and are take up through a MCT transporter
within there target cell
T4 is covered to T3 by a deiodinase enzyme
there are 2 classes od deiodinase enzyme
- 5 prime 3 prime deiodinases (5’/3’)
- 5 non prime 3 non prime deiodinases (5/3)
5’/3’ deiodinase coverts
T4 to T3 by removing an iodine molecule from the outer tyrosine molecule
5/3 deiodinase converts
T4 to reverse T3 (rT3) by removing an iodine molecules from the inner tyrosine molecule
what is reverse T3
inactive form of T3
how many types of 5 prime 3 prime deiodinases are there
3
type 1 deiodinase (D1)
found in the liver and the kidneys
type 2 deiodinase (D2)
found in the heart, skeletal muscle, CNS, fat, thyroid and pituitary gland
type 3 deiodinase (D3)
found in fatal tissue, placenta and the brain (except in the pituitary)
after deiodination the T3 then
binds to the thyroid hormone receptor within the nucleus to form the thyroid hormone complex together with retinoid receptor X then binds to the thyroid response element on the promotor region of target genes and influences transcription of the downstream gene
the whole process either
activates or represses the transcription of genes that regulate basal metabolic rate and development
there are different
thyroid hormone receptors isoformes present in different tissues
types of thyroid hormone receptors
- thyroid hormone receptor alpha 1 and alpha 2
- thyroid hormone recepto beta 1 and beta 2
where is thyroid hormone receptor alpha expressed
predominantly in the heart, intestine, bone and skeletal muscles
where is thyroid hormone receptor beta predominantly expressed
brain, liver, hypothalamus and pituitary
resistance to thyroid hormone alpha caused by
mutation in THRA leasing to defective signalling through the THR alpha receptor
resistance to thyroid hormone alpha causes
tissue specific hypothyroidism but near normal thyroid function tests because the feedback loop is normal
symptoms of resistance to thyroid hormone alpha
delayed bone development, chronic constipation, impairs neural and cerebellum development and bradycardia
resistance to thyroid hormone beta caused by
mutation in THRB leading to defective signalling through the THR beta receptor
resistance to thyroid hormone beta causes
elevated T3 and T4 and TSH levels because the THRB receptor is expressed in the pituitary and hypothalamus
resistance to thyroid hormone receptor beta is more
common than resoatcne to thyroid hormone receptor alpha
presentation of resistance to thyroid hormone beta
goitre, abnormal cochlear development, affects colour vision, tahcycardia, impaired neural development
physiological affects of thyroid hormone
- increases basal metabolic rate
- increases thermogenesis
- increases carbohydrate metabolism
- increases lipid and protein metabolism
how does thyroid hormone increase basal metabolic rate
- increases the number and the size of mitochondria
- increases oxygen used and rate of ATP hydrolysis
- increases synthesis of repsiratory chain enzymes
how does thyroid hormone increase thermogenesis
30% of temperature regulation is due to thyroid hormone thermogenesis
how does thyroid hormone increase carbohydrate metabolism
- increases blood glucose due to stimulation of glycogenolysis and gluconeogenesis
- increases insulin dependant glucose uptake into cells
how does thyroid hormone increase lipid and protein metabolism
- mobilises fat from adipose tissue and increases fatty oxidation in tissues
- increases protein synthesis
the production and secretion of what required thyroid hormone
growth hormone releasing hormone and glucocorticoid induced growth hormone releasing hormone
what else requires thyroid hormones
development of foetal brain, as myelinogenesis and axonal growth require thyroid hormone
if hypothyroidism is untreated during pregnancy what happens
the neonate has a marked reduction in IQ
thyroid hormones are required for normal
central nervous system activity
thyroid hormones increase the
number of receptors for adrenaline and noradrenaline which increases the force and rate of cardiac contraction
