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Regulation of calcitonin secretion

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. Response to calcium Calcium receptors

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Regulation of calcitonin secretion

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  1. 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

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

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

  4. 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

  5. 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)

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

  7. Synthesis • Vitamin D2 (ergocalciferol) • Precursor • Ergosterol • Plant origin

  8. 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

  9. 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

  10. 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

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

  12. 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

  13. 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

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

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

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

  17. 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

  18. Hormonal integration in calcium homeostasis • Calcitonin • Inhibition of PTH and vitamin D action on osteoclasts • Not on osteoblasts

  19. 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

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

  21. 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

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

  23. 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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