Thyroid Gland Flashcards
Metabolically active hormones of thyroid gland
Thyroxine 93% T4
Triiodothyronine T3 4x as potent but less
Calcitonin
Major constituent of colloid of thyroid glands
thyroglobulin containing thyroid hormones
Amount of iodine ingested each year for hormone formation
50mgc
1mg/wk
Thyroid hormone formation:
iodide trapping formation and secretion of thyroglobulin oxidation of iodide ion iodination of tyrosine and formation of thyroid hormones aka organification storage of thyroglobulin release of T4 and T3
First stage in formation of thyroid hormone
Transport of iodide from blood to thyroid cells
via this symporter
Iodide trapping
Sodium-iodide symporter
Sodium-iodide symporter co transports
1 iodide ion
2 sodium ions
from the lon Na gradient by Na-K ATPase
Rate of iodide trapping is influenced by
TSH concentration
Iodide is transported out of the thyroid cell into the follicle by the counter transporter
pendrin
chloride-iodide ion countertransporter
Major substrates in thyroglobulin that combine with iodine to form hormone
tyrosine AA
First essential step in formation of thyroid hormones
Conversion of iodide ions to iodine (I0 or I3) aka oxidation which is capable of combining with tyrosine
Oxidation of iodine is promoted by the enzymes
Peroxidase with
hydrogen peroxide
Binding of iodine with tyrosine in thyroglobulin is called
organification
Final formation of two important hormones
1 tyrosine iodized to monoiodotyrosine and to diiodotyrosine
2 more iodotyrosine coupled (diiodo)
2 mol diiodo T4
1 mol monoiodo with 1 mol diiodo T3
During release of T3 and T4, thyroglobulin is cleaved via
proteases
Remaining iodine trapped with unreleased thyroglobulin is cleaved by to be recycled
deiodinase enzyme
Once released in blood, T4 and T3 combine with
TBG
Thyroxine binding prealbumin
Albumin
T4 is released slowly into target tissues every
While T3 is released bec of lower affinity in about
6 days with long latent period
1 day
General effect of thyroid hormones are to
this is done by
activate nuclear transcription of large numbers of genes
removing one iodide from all thyroxine forming T3 which has affinity to about 90% of peripheral receptors
on the DNA to activate nuclear receptors, the hormone forms a heterodimer with
RXR
retinoid X receptor at thyroid hormone response elements
Transcription initiated
Translation then formation of hundreds of intracellular proteins
T4 is converted into T3 by
Iodinase
Effect of thyroid hormone on metabolic activity
Increased by 60-100
Inc protein synth and cata
TH on mitochondria
Increase in size and number
Inc rate of ATP formation
TH on active transport of ions
Inc activity of Na/KATpase
TH on growth
Increased
Important in brain development in fetal life
TH on carbohydrate metabolism
Inc uptake, glycolysis, gluconeogenesis, rate of absorp, insulin secretion
Effect of TH on fat
Inc mobilization
Inc FA conc in plasma and oxidation
Dec conc of chole, phospholipid and TAG in plasma despite FA inc
Excess in TH may cause
vitamin deficiency
TSH effect on thyroid gland
1 inc proteolysis of thyroglobulin
2 inc activity of iodide pump
3 inc iodination of tyrosine
4 inc size and secretory activity of thyroid cells
5 inc number of thyroid cells plus change from cuboidal to columnar
TSH activation
TSH binding with receptor on thyroid gland
Activation of adenylate cyclase
Inc cAMP formation (as 2nd messenger)
Mult phosphorylations
TRH acts to produce TSH by
binding to TRH receptors in anterior pituitary
Activating PLC
Cascade of Ca ions + DAG
TSH release
Thiocyante, perchlorate and nitrate ions dec thyroid secretion by
decreasing iodide trapping by competitive inhibition of NIS
no effect on thyroglobulin
Inc TSH -> goiter
PTU, Methimazole and Carbimazole dec thyroid supression by
Preventing formation of thyroid hormones from iodides and tyrosine
Blocking of peroxidase for iodination of tyrosine and coupling of two iodinated tyrosine
No effect on thyroglobulin
Inc TSH -> goiter
Iodides dec thyroid activity by
Decreasing all phases of thyroid activity esp at release of thyroid hormones
Dec size of thyroid gland utilized preop