Lec 8 - Thyroid hormones Flashcards
what are thyroid hormones derived from
tyrosine
3 types of thyroid hormones
Thyroxine = T4
Triiodothyronine = T3
Reverse T3 = inactive
why does T4 need binding proteins to transoprt it in serum
is insoluble
why can liver disease lead to loss of effective t4 transport
this is where binding proteins are synthesised
3 types of T4 binding proteins
- albumin
- transthyretin (ttr)
- Thyroxine binding protein (TBG)
most abundant t4 binding portein
thyroxine binding globulin
70-75%
how much T4 does albumin hold in plasma
5-10%
how much t4 does TTR bind (and where does it deliver to)
20%
delivers to CNS
where is T4 converted
in peripheral tissues
which binding protein has highest affinity for t4
TBG
which bindning protein has highest capacity for t4
albumin
but since has lowest affinity = holds the least
which of the binding proteins ONLY binds t4 and not t3
TTR
what hormone increases TBG
oestrogen
which is why in nearly doubles in conc during pregnancy
what lowers concs of TBG
corticosteroids
illness
stress
cirrhosis
nephrotic disorders
which transporters move free t4 and t3 into cells
MCT8
MCT10
OATP1c1
which enzymes convert T4 to T3
iodothyronine deiodinases (DIO)
(1, 2 and 3)
which DIO makes the most circulating T3
DIO1
where is DIO1 predominately found
liver
kidney
muscle
where is DIO2 found
areas of CNS
and
pituitary thyrotropes
what kind of T3 does DIO2 make
intracellular T3
DIO3 function
produces reverse T3
- prevents thyroid hormone accessing specific tissues
what is the 2 thyroid hormone receptors and where are they
TRalpha and TRbeta
- found in nucleus
what do TR form a dimer with
retinoid X receptor (RXR)
where does TR and RXR bind
to thyroid resposive element
on DNA
(hard to explain, see onenote)
how does T3 affect growth hormone
the gene encoding growth hormone is responsive to T3
= increases gene expression
in what situation would T3 binding actually lead to gene inhibition
in gene coding for expression of alpha and beta subunits of TSH
(mechanism of negative feedback)
5 biological actions of thyroid hormone
- control basal metabolic rate
- growth regulating role
- foetal development
- cardiovascular effects
- musculoskeletal effects
3 things thyroid hormone does to affect basal metabolic rate
- increases proteins for tissue growth and maturation
- increases expression of Na+/K+ ATPase
- increases mitochondria (stimulating mt replication) and respiratory enzymes
what are the effects on cardiac when increased thyroid hormone
more O2 needed
to supply increase in metabolism
so cardiac output and ventilation increases
what does loss of t4 in foetus lead to
irreversible intellectual disability and dwarfism
effect of iodine deficiency in foetus
- miscarriage/stillbirth
- congenital abnormality
effect of iodine deficiency in foetus
neonatal goiter
neonatal hypothyroidism
intellectual disability
iodine decifiency in child/adolecsent
subclinical goiter hypothyroidism
impaired mentla funciton
delayed phsyical development
what does T3 increase in terms of cardiovascular effects
- cardiac contraction and output
- heart rate
- increased O2 supply to tissues
- inc CO2 removal from tissues
3 direct effects of T3 in CV system
- inc myocardial Ca2+ uptake
- inc expression of alpha-myosin heavy chain and decreased beta
- increased expression of RYR in SR
indirect effects of T3 on CV system
- increased metabolism = inc thermogenesis = vasodilation
- inc sensitivity to catecholamines
how does t3 have musculoskeletory effectsq
