Regulation of calcitonin secretion

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Regulation of calcitonin secretion

• Elevation of blood calcium
• Response greater in male
• Affected by age
• Declines as one ages
• Secretion by GI tract
• Gastrin
• Stimulator of acid secretion
• Cholecystokinin

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• Response to calcium
• Calcium receptors
• Increased calcium, increased calcitonin secretion

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Physiological roles

• Bone mineral metabolism
• Prevention of hypercalcemia
• After meals
• Mineralization of bones in neonates
• Protection against calcium loss
• Pregnancy
• Lactation

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• Satiety factor
• Regulation of food intake
• Inhibition of food intake
• Inhibition of calcium-induced hunger
• Vitamin D regulation
• Stimulation of vitamin D metabolism
• Direct stimulation
• Decreased blood calcium level

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Mechanism of action

• Receptors for calcitonin
• Skeletal tissue, kidneys, and Leydig cells
• Coupled with adenylate cyclase
• Coupled with different types of G proteins
• Gs, Gi, and Gq
• Depending on the cell cycle
• Trigger different responses (activation of
  different sigaling pathway)

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Vitamin D

• Cholesterol derivative
• Contain sterol ring
• Two substances
• Cholecalciferol
• Ergocalciferol
• Not really vitamin
• Precursor for steroid-like hormones
• Produced by specific tissues

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Synthesis

• Vitamin D2 (ergocalciferol)
• Precursor
• Ergosterol
• Plant origin

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• Vitamin D3 (cholecalciferol)
• Produced by skin
• 7-dehydrocholesterol
• UV light as energy source (thermal isomerization)
• Production of inert metabolites (lumisterol and
  tachysterol) when exposed to sun for a prolonged
  period
• Transported into the blood
• Vitamin D3 only
• Binding protein
• Transcalciferin

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• Vitamin D3
• Requires further conversion
• 25-hydroxyvitamin D3
• Liver
• 1,25-dihydroxyvitamin D3
• Kidneys
• Hormonal form of vitamin D3
• Bound to plasma protein (transcalciferin)
• 24,25-dihydroxyvitamin D3
• Inactive form in mammals
• Kidneys and other organs
• 1,24,25-trihydroxyvitamin D3
• Unknown origin and function

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Vitamin D metabolism

• Blood calcium level
• Production of 1,25 dihydroxyvitamin D3
• Increased when low blood calcium level
• Decreased when high blood calcium level
• Regulated by PTH
• Production of 24,25 dihydroxyvitamin D3
• Increased when 1,25 dihydroxyvitamin D3 decreases
• Inhibited by PTH

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• Activity of renal 1alpha-Ohase
• Regulation
• Vitamin D level (inverse)
• PTH (stimulation)
• Inhibited by 1,25 dihydroxvitamin D3
• Increased phosphate excretion (stimulation)
• PTH-induced

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• Conversion of 25-hydroxyvitamin D to 24,25
  dihydroxyvitamin D
• Inactivation of 25-hydroxyvitamin D
• Secretion of 1,25 dihydroxyvitamin D3
• Hormonal regulation
• Insulin
• GH
• Prolactin

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Physiological roles

• Absorption of calcium
• Intestine
• Increased phosphate translocation
• Increased calcium transport
• From mucosa to serosa via cytosolic calcium
  binding protein
• Bones
• Paradox
• Essential for normal bone growth
• Causes demineralization

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• Absorption of calcium
• Kidneys
• Tubular reabsorption
• Retention of phosphate by proximal tubule

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• Regulation of PTH secretion
• Negative feedback
• Long-feedback system
• Blood calcium level
• Short-feedback system
• 1,25 dihydroxyvitamin D3

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• Proliferation and differentiation of cells
• Hematopoetic stem cells
• Keratinocytes
• Myoblasts
• Immune reaction

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Mechanism of action

• Receptor
• Nuclear receptor
• Similar to steroid receptor
• Ligand binding domain
• DNA binding domain
• Interaction with hormone responsive element
• VDRE
• Delayed action (2 hours)
• Protein synthesis

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Hormonal integration in calcium homeostasis

• Calcitonin
• Inhibition of PTH and vitamin D action on
  osteoclasts
• Not on osteoblasts

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Hormonal integration in calcium homeostasis

• Calcitonin
• Inhibition of bone resorption by multinucleated
  osteoclast
• Alteration of morphology
• Activity of osteoclast activity
• Reduced lysosomal enzyme release
• Stimulates detachment of osteoclasts
• Inhibit motility
• Reduction of lifespan

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• PTH
• Elevation of blood calcium level
• cAMP mediated
• Stimulation of osteoclast activity
• Inhibition of osteoblast activity
• Osteoblast
• Target cells
• Indirectly affect osteoclast function

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• PTH
• Stimulates secretion of osteoclast
  differentiation-inducing factors
• Cytokines
• IL-6
• Increased differentiation of precursor cells into
  multinucleated osteoclasts
• Morphological changes
• Secretion of lysosomal contents
• Result in increased release of calcium and
  phosphate

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• Regulation
• Short-term
• Parathyroid gland
• PTH
• Long-term
• Kidney
• 1,25-dihydrovitamin D
• Intestinal calcium absorption
• Decreased skeletal calcium turn-over

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• Other hormones
• Estrogens
• Crucial for maintenance of bone density in women
• Inhibition of IL-6 secretion
• GH
• Greater bone mass in African-Americans

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