L3 Thyroid Hormone Flashcards

(10 cards)

1
Q

Synthesis of T3 and T4 (basics)

A

Synthesized from tyrosine residues on thyroglobulin (TG)
- Requires dietary iodide
- Synthesis controlled by TSH
T3 = triiodothyronine (biologically active)
T4 = thyroxine (preferential synthesis, prohormone)
Reverse T3 also produced, biologically inactive

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2
Q

Iodide transport and storage

A
  • Most is stored in the thyroid gland
  • Concentrated in gland by a 2Na+/I- symporter (no ATP)
  • Gland can autoregulate iodide transport according to needs
  • Chronic iodide deficiency can lead to hypothyroidism (problem in landlocked areas) - can be corrected with dietary supplements
  • Most is associated with colloidal TG
  • Ultimately TH is metabolized and iodide is excreted
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3
Q

Steps of TH synthesis and storage

A
  1. Thyroglobulin (TG) are produced in ER, packaged into vesicles, exocytosed into follicle
  2. I- enters thyrocyte and rapidly associates with apical membrane
  3. In follicular lumen, I- is oxidized to iodine by thyroid peroxidase and is put on tyrosine residue on TG (replaces H+)
  4. MIT: binding of one Iodine, DIT: binding of two iodine (called organification). Tyrosine perioxidase also combines DIT+DIT to make T4. Also some T3 is made (DIT+MIT)
  5. Endocytosed back into cell and stored as colloid
  6. Colloid proteolysis is stimulated by TSH. DIT and MIT reenter pool for more synthesis, T3 and T4 released into blood
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4
Q

Thyrocyte response to TSH

A
  • Secretes T4 (93%) and T3 (7%)
  • Most circulating TH is bound to TBG (70%), other binding proteins are transthyretin and albumin
  • Free TH is what circulates (~0.03 T4 and 0.3% T3) and enters tissues –> binds to receptor on the thyroid response element (TRE) of gene –> T3/T4 binding regulates transcription of these genes
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5
Q

How is T3 generated from T4?

A
  • T4 is metabolized by peripheral deiodinases
  • Antithyroid agents (used to tx hyperthyroidism) inhibit the conversion of T4 to T3
  • T4 is used to treat hypothyroidism because of its longer half-life and greater stability
  • THs have slow onsets and long duration of action
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6
Q

Effects of thyroid hormone

A
  • Increase metabolic rate of O2 consumption
  • Important for BMR (increases in hyper and decreases in hypothyroidism)
  • Acts with GH and somatomedins to promote bone formation
  • Promote ossification and fusion of bone plates/maturation
  • Essential for CNS development in perinatal period - TH deficiency in infants results in mental and growth retardation
  • Treat with thyroxine/T4
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7
Q

Physiological effects of low levels of thyroid hormone

A
  • Decreased BMR
  • Carbohydrate metabolism: decreased gluconeogenesis and glycogenolysis, normal serum [glucose]
  • Protein metabolism: decreased synthesis and proteolysis
  • Lipid metabolism: decreased lipogenesis, lipolysis, increased serum [cholesterol] - increased risk for arteriosclerosis
  • Decreased thermogenesis
  • Normal levels of serum catecholamines
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8
Q

Physiological effects of high levels of thyroid hormone

A
  • Increased BMR
  • Carbohydrate metabolism: increased gluconeogenesis and glycogenolysis, normal serum [glucose]
  • Protein metabolism: increased synthesis and proteolysis, muscle wasting (proteolysis outweighs synthesis)
  • Lipid metabolism: increased lipogenesis, lipolysis, decreased serum [cholesterol]
  • Increased thermogenesis
  • Increased expression of beta adrenoreceptors (increased sensitivity to catecholamines, which remain at normal levels). Beta adrenergic antagonists can treat hyperthyroidism symptoms
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9
Q

What is thyroid function regulated by?

A
  • Hypothalamic TRH (+): stim TSH release through GPCR linked to PLC/IP3/intracellular Ca
  • Anterior pituitary TSH (+): stim TH release through GPCR linked to adenylate cyclase and cAMP
  • Circulating T3 and T4 (-): negative feedback
  • Dopamine and somatostatin inhibit TSH release
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10
Q

How is primary thyroid disease diagnosed?

A
  • Determination of serum TSH
  • Elevated in primary hypothyroidism due to lack of negative feedback by low circulating T3 and T4
  • Reduced in hyperthyroidism due to excessive negative feedback by high circulating T3 and T4
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