Thyroid Hormones Flashcards
which thyroid hormone is dominant?
T3- 85% of thyroid hormone bound to thryoid receptor is T3
T3 has a 10x greater affinity for TR than T4
many peripheral tissues convert T4 into T3 for their use
describe the thyroid receptor
TR is in the nucleus, and thyroid hormone binds there directly (as a dimer w/ RXR or RAR)
their are 2 subtypes- alpha and beta, coded for by 2 different genes
thyroid response element
the coding sequence on the genome where the TR binds
what changes does the binding of TH cause in the cell?
increases mRNA transcription
unbound HR causes transcription inhibition (ie not inert)
symptoms of hypothyroidism
weakness dry skin coarse skin lethargy slow speech edema of eyelids sensation of cold reduced sweating cold skin
symptoms of hyperthyroidism
nervousness increased sweating intolerance to heat palpitations fatigue weight loss tachycardia dyspnea
most common cause of hyperthyroidism
graves disease- autoimmune
goiter, eye symptoms, and hyperthyroidism
describe the physiologic effects of TH
metabolic
- basal metabolic rate
- heat production
- water/ion transport
- calcium and phosphorus metabolism
- cholesterol and fat metabolism
- nitrogen turnover
- increases GI tract activity
- increases CV (HR) and respiratory
all above is reversible w/ replacement therapy
growth and development
- growth of tissues
- development and maturation of CNS
these are not reversible changes
describe lack of TH during development (hypothyroidism)
- impaired brain development
- limited growth
- ataxia
- spastic muscles
- deafness
not reversible
what is the outcome like for people born w/ congenital hypothyroidism and receive adequate replacement therapy immediately?
seemingly normal
how does the fetus receive TH?
the mother supplies TH to the fetus until they are able to make it themselves
if the mother TH is inadequate and untreated, it often leads to infertility
most important cause of preventable mental defects in the world
iodine deficiency
neurological cretin
people who do not receive TH from their mother d/t iodine insufficiency
how?
with low iodine supply in the mother, thyroid shifts primarily to T3. T4 is better at crossing the placenta and better at reacting w/ brain. fetus lacks this.
causes:
major CNS damage
fetal thyroid function is impaired, but could be restored w/ iodine postnatally
hypothyroid goiter
thyroid cannot make thyroid hormone properly, (iodine deficiency), so no feedback on TSH, which gets continuously secreted and causes growth in the thyroid
hyperthyroid goiter
graves disease- autoAb binds the TH continuously and causes growth
which form of TH is essential for fetal development?
t4- it crosses the placenta
Pax8 mice
born w/o Pax8 gene, which is essential for thyroid growth. therefore no thyroid
appear normal at birth: growth is retarded poor coordinatoin deaf poor hair growth do not survive beyond weaning
do unliganded TR have effects?
yes- negative inhibitory effects
describe biosynthesis of TH
iodide gets concentrated inside follicular cells inside the thyroid
tyrosine residues in thyroglobulin take up one or two iodides to form monoiodotyrosine or diiodotyrosine.
coupling of these molecules forms T3 or T4, w/ T3 favored.
hydrolysis of thyroglobulin yields T4 and T3 (and MIT and DIT)
T3 and 4 are released into the blood
MIT and DIT are retained in the thyroid and deiodinated
thiouracil, methimazole
inhibit conversion to iodine and creation of MIT and DIT
is iodide trapping energy dependent?
yes
5’deiodinases
convert T4 to T3 in periphery
perchlorate, thiocyanate
inhibit iodide trapping
describe the control of TH release
-excess dietary iodine suppresses synthesis and release of TH (independent of TSH). likewise, decrease in plasma iodine results in increased uptake.
TSH- main physiological regulator
pathological examples
- thyroid stimulating ABs
- TSH binding- inhibiting Abs
- hCG (stimulates)
