Flashcards in The Thyroid Gland Deck (60)
Where is the thyroid gland?
wrapped around the trachea
How is the thyroid gland structured?
follicles lined with epithelial thyrocytes which are spherically arranged
What cells are in the thyroid gland?
C -cells which are parafollicular and thyrocytes
What does the thyroid gland secrete?
T3, T4 and calcitonin
What are the proportions of thyroid hormone produced?
T3-10%, reverse T3-1% and T4-90%
T3 is more potent than T4
How is T4 converted to T3?
a deiodinase enzyme found in peripheral tissues
What is the action of T3?
binds to high affinity T3Rs (TRa and TRb) associated with DNA in cell nucleus -> activate or represses gene transcription and thus regulate mRNA synthesis and protein synthesis
What are the features of the different types of deiodinases?
Type 1 - low affininty 10microM km, occurs in tissues with high blood flow and plasma exchange...i.e. liver, kidney and skeletal muscle, supplies circulating T3 for uptake by other tissues
Type 2 - high affinity 1nanoM km, expressed by glial cells in the CNS, provides T3 even when T4 levels are low, present in the thyrotropes of the pituitary acting as a thyroid axis sensory
Where does thyroid hormone biosynthesis occur?
Within the colloidal cavity
What does TH biosynthesis require?
thyroglobulin - secreted into follicle colloid
iodine ions - transported into follicular cells by Na-I symporter and into colloid by pendrin
What transports I into the colloid?
What is iodination?
adding iodine to thyroglobulin
How is thyroglobulin made into thyroid hormone after iodination?
endocytosed into vesicles and then fuse into lysosomes which degrade the tyrosine molecules into thyroid hormones
which enzyme catalyses the synthesis of thyroid hormones?
What processes does thyroid peroxidase catalyse?
coupling sequential reactions
What are the carrier proteins that thyroid hormones bind to?
thyroxine-binding globulin - major TBG
transthyretin - delivering to CNS - minor
How much iodine is ingested and excreted everyday?
150micrograms in adults
90-120micrograms in children
200micrograms in pregnant women
how much iodine is taken up by the thyroid gland?
what is the total iodide content of the average thyroid?
7500micrograms - about 70-80 micrograms is released daily
Where is iodide actively concentrated?
thyroid gland, salivary glands, gastric glands, lacrimal glands, mammary glands and choroid plexus
What can stimulate thyroid hormone secretion?
Low BMR, cold
What can inhibit thyroid hormone secretion?
trauma, stress, T3 - ant. pit/hypothalamus, T4 - ant. pit./hypthalamus and TSH - hypothalamus
What pathways does TSH stimulate at the thyrocytes?
Gs -> Ac -> PKA
Gq -> PLC -> PKC and Ca[i]
What does the stimulation by TSH result in?
increased iodide uptake
increased synthesis of peroxidase
increased synthesis of thyroglobulin
increased colloid uptake
what is the Thyroid receptor?
a nuclear receptor that regulates transcription
How does the thyroid receptor function?
as a heterodimer with the retinoic acid X receptor, TR-RXR binds to the thyroid response element on target gene
What happens with TR-RXR in the absence of TH?
represses gene transcription through recruitment of a compressor complex containing histone deacetylase (HDAC)
What happens with TR_RXR in the presence on TH?
coactivator complexes including histone acetyl transferase, increased acetylation and promotes transcription
What binds RXR?