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TH effects on brain development

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TH effects on brain development. Exerted through enhancement of nerve growth ... Decreased myelinogenesis, axonal outgrowth. Decreased protein synthesis. Thermogenesis ... – PowerPoint PPT presentation

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Title: TH effects on brain development


1
TH effects on brain development
  • Exerted through enhancement of nerve growth
    factor (NGF) production?
  • Lack of TH gt cretinism
  • Causes of cretinism
  • Hypothyroidism during development
  • Maternal iodine deficiency
  • Result
  • Decreased myelinogenesis, axonal outgrowth
  • Decreased protein synthesis

2
Thermogenesis
  • Homeotherms require mechanisms for generating
    heat
  • Sodium pump theory of thermogenesis
  • Na/K ATPase
  • Extrudes 3 Na ions takes in 2 K ions
  • Requires ATP to move Na against electrical
    gradient
  • Heat is given off as phosphate bond is broken in
    ATP

3
Thermogenesis, contd.
  • TH indirectly fuels this process thru its
    mitochondrial actions
  • Inhibit Na/K ATPase with ouabain gt reduce TH
    effects on heat production
  • genomic effects of TH also contribute
  • Increases number of Na/K ATPases in plasma
    membrane
  • Increases expression of mitochondrial enzymes

4
Hypothyroidism
  • Conditions of insufficient TH production
  • 2 types
  • Primary origin (thyroid problem)
  • Secondary origin (problem elsewhere in thyroid
    axis)
  • Cretinism deficiency during embryonic
    development gtimpaired somatic, intellectual dev.
  • Myxedema deficiency during adulthood

5
Causes of hypothyroidism
  • Iodine deficient diet
  • Failure in thyroid development
  • Thyroid dyshormonogenesis (failure to produce
    appropriate enzymes)
  • TSH receptor mutations (inactivating)
  • TRH receptor mutations (inactivating)
  • Low T3 syndrome (failure of peripheral conversion
    of T4 to T3)

6
TH receptor defects
  • Often, physical symptoms resemble hypothyroid
    state
  • Exception elevated TH levels
  • Types
  • Generalized resistance to thyroid hormone (GRTH)
  • Selective peripheral resistance to thyroid
    hormone (PerRTH)
  • Selective pituitary resistance to thyroid hormone
    (PRTH)

7
Hyperthyroidism
  • Thyrotoxicosis (excess TH production)
  • Symptoms
  • Increased metabolic rate
  • Rapid pulse, elevated body temperature
  • Nervousness, anxiety
  • Primary origin
  • Neoplasia
  • Activating TSH receptor mutation
  • Secondary origin
  • TSH-producing tumors
  • Thyroid-stimulating antibodies

8
Graves Disease
  • Overstimulation of thyroid
  • Autoimmune response
  • Previously thought to be caused by thyroid
    stimulating antibodies (TSAb)
  • TSAb can activate TSH receptor
  • Associated with exophthalmos
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