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13 Cards in this Set
- Front
- Back
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Thyroid hormones |
most: 3,5,3',5'-tetraiodothyronine (thyroxine, T4) 3,5,3'-triiodothyronine (T3) 3,3',5'-triiodothyronine (reverse T3) 3,3'-diiodothyronine (T2) - both positions on the inner ring need to be filled w/ I -> active - Peripheral tissues: T4 -> T3 (TR-binding) & rT3 - Metabolic processes control, heat production, normal growth & development |
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Mechanism of TH action |
T4 & T3 -> TH transporters (MCTs, OATPs) -> cells -> Nuclear TH R's (T3 > T4) -> TRE's TR in absence of TH -> opposite effect => absence of R -> processes less suppressed, just slower - myelin, malic enzyme, myosin, ... |
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Biosynthesis of TH |
- Na-I symporter (NIS) -> plasma I in thyroid BM - I- -> peroxidation -> I2/I+ (iodinating agent) - thyroglobulin -> Tyr iodination -> Mono- & Di-I Tyr (MIT & DIT) - 2DIT/MIT+DIT -> T4/T3 - TG hydrolysis -> T4, T3, MIT, DIT; T4 -> T3 - MIT & DIT -> iodotyrosine deiodinase -> Tyr, I - T4, T3 released |
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TH Synthesis & Secretion Control |
Autoregulation: ↑I --| (!) NIS, T4, T3 release [temporary] Extrathyroidal regulation: TRH (hypothalamus) -> TSH (pituitary) -> TSH-R (thyroid) ->> cAMP ->> - hormone biosynthesis & secretion - thyroidal intermediary metabolism - phospholipid & RNA synthesis, growth, vascularity Pathological thyroid regulators: Thyroid-stimulating Ig's, TSH-binding-inhibiting Ig's, hCG |
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TSH Synthesis & Secretion Control |
TRH (hypothalamus) -> AP R's -> PIP2 (phosphatidylinositol 4,5 bisphosphate) -> TSH synthesis & release -fb: T4, T3 -> -| (hyp.) TRH release -| (AP) TSH-a/TSH-b (subunits) production & release, X TRH (↓ TRH-R) |
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TH in circulation |
- Mostly T4, some T3, traces of rT3 > 99.5% bound to plasma proteins: TBG (60%; T4>T3), TBPA (T4; 30%), albumin (T4,T3; 10%) - only unbound is physiologically active & regulated (TBG deficiency -> loooow total TH) |
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TH binding |
Nuclear R's: a1, a2 (does not bind T3), b1, b2 Non-R P's: extracellular fluids, PM, cytosol, nucleus - low affinity (T4>T3) & high capacity - no hormone action |
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Peripheral distribution & metabolism of TH |
Present in all tissues Metabolized by 3 deiodinases (D = inner ring; D' = outer ring): D1 (5'-D) - liver, kidney, thyroid; T4 -> T3, rT3 -> T2 (-> plasma; non-ess.) D2 (5'-D) - pituitary, CNS, brown fat; T4 -> T3, rT3 -> T2 (local; essential) D3 (5-D) - placenta, pregnant uterus, developing brain; T4 -> rT3; T3 -> T2 (both inactive) Liver: conjugation w/ glucuronic A & sulfate -> bile -> partially hydrolysis -> TH -> reabsorption |
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TH-driven regulation |
BMR & heat production H2O & ion transport Ca & P metabolism Cholesterol & fat metabolism (obesity) N2 metabolism Carbohydrate metabolism Systems: CV (HR), Resp., GI, sM.'s, NS |
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TH-driven growth & developmental effects |
Vertebrate tissue growth Amphibian metamorphosis CNS maturation |
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TH deficiency effects |
Hypothyroidism: Mental retardation = cretinism (congenital: irr.) Stunted growth, ataxia, spastic musles, deafness Mother's I deficiency during pregnancy -> neuro dmg During pregnancy - TH from mother Treated right after birth -> normal development |
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Hypothyroidism symptoms |
- more common in women, symptoms reversible - I deficiency -> preferential production of T3 - weakness, dry skin, lethargy, edema/eyelids, sensation of cold, goiter, problems concieving |
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Hyperthyroidism symptoms |
- more common in women, symptoms reversible - Graves' Disease (TSH lo; Ab -> hyperthyroidism -> goiter, eye symptoms) - nervousness, increased sweating, intolerance to heat, palpitations, fatigue, weight loss |
