5: Thyroid Hormones - Wilson Flashcards
leading cause of preventable brain damage worldwide
iodine deficiency
large hemodimeric glycoprtn made in follicular cells and secreted through the apical membrane forming a major component of colloid
thyroglobulin
source of iodine
diet (comes in the form iodide)
low dietary iodine –>
goiter
enlargement of thyroid gland to better scavenge low levels of iodine
-persistnetly elevated TSH drives growth
incorporation of iodine into thyroglobulin =
organification of iodine
- catalyzed by throid peroxidase on apical membrane
- uses iodide ions to reduce H2O2 (produced by NADPH oxidase) to water
more T_ is formed than T_
more T4 is formed than T3
about ____ molecules of thyroid hormone are formed per thyroglobulin dimer
2-5
small amounts of iodinated thyroglobulin enter the serum via…
transcytosis
easy to measure in the clinical laboratory
levels will increase with graves disease and thyroiditis
______ of the hypothalamus release TRH
parvicellular neurons
thyrotropin =
TSH (different name for same thing)
__ and _____ inhibit TSH secretion
somatostatin and dopamine
__ binds to thryorid binding globin more tightly than ___ —?
T4 tighter than T3
contributes to longer half-life of T4 compared to T3
the biologically active form of T3/4 is the _____
free form - not the bound form (more T3 is free- T3 is more biologically active )
80% of circulating T3 is generated by…
deiodinase reactions of T4
major sites of deiodination are liver and kidney
major source of circulating T3
type I deiodinase
production of t3 in peripheral tissues
important in the control of thyroid hormone release
type II deiodinase
converts t4->t3
important in tissues that generate t3 locally from t4 rather than acquiring from the circulaiton
considered to be major physiological terminator of thyroid hormone action in peripheral tissue
type III deiodinase
does not convert T4 to T3 (makes rT3 or T2)
high t3 will induce expression of type III deiodinase
facilitates elimination in bile
glucoronidation of thyroid hormone in liver
lack of thyroid hormone during development leads to …
mental retardation, growth, and developmental delay
how does thyroid hormone increase basal metabolic rate?
- increase transcription of Na/K ATPase
- stimulated transcription of mitochondrial uncoupling prtn –> release heat
how does thyroid hormone regulate carbohydrate and lipid metabolism?
- enhance carbohydrate absorption and oxidation
- stimulate glycogen breakdown and gluconeogenesis
- stimulate lipolysis
- stimulate cholesterol synthesis/degradation
hematopoietic effects of thyroid hormone
- increased erythropoietin production
- increased 23bisphospholglycerate content of erythrocytes
GI effects of thyroid hormone
increased gut motility
graves disease =
autoimmune disease with antibodies binding to TSH receptor –> hyperthyroidism
hashimoto’s thyroiditis =
autoimmune disease with antibodies to thyroid peroxidase, thyroglobulin, TSH receptor blocking antiboies –> decrease hormone production and secretion
in the absence of bound thyroid hormone, thyroid hormone receptor/RXR complex…
recruits a histone deacetylase –> condensation of chromatin and inhibition of transcription
binding of thyroid hormone triggers conformation change in thyroid hormone receptors …
HDAC released and HAT binds in its place –> leads to relaxation of chromatin and enhancement of transcription
what thyroid hormones work with mitochondrial bioenergetics?
T2
what mitochondrial hormones are responsible for alterations in actin cytoskeleton?
T4 and rT3
