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Calcium Homeostasis: Hormones, Growth, Balance

Explore the role of hormones like Parathyroid Hormone, Vitamin D, and Calcitonin in regulating bone growth and calcium balance. Learn about key processes and receptors involved in responding to low calcium levels, as well as the effects on bone density. Discover the significance of Vitamin D activation and its impact on calcium absorption.

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Calcium Homeostasis: Hormones, Growth, Balance

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  1. Lecture # 12: Calcium homeostasis • Hormones that regulate bone growth and calcium balance • Parathyroid Hormone • Vitamin D • Calcitonin

  2. Announcements • Mini-exam #3 – Wed – sex diff, calcium • Genes & Genomes • Thurs 1:30-5:00 Brown & Goldstein

  3. Food 1000 Feces 850 Small intestine 150 300 500 ECF 500 Cells Bone 8000 7850 Nephron Urine 150

  4. variable variable Set point Effector Sensor, receptor Integrator, controller

  5. Blood Ca+2 Blood Ca+2 Set point Effector Sensor, receptor Integrator, controller

  6. Blood Ca+2 Blood Ca+2 Set point Effector Sensor, receptor Integrator, controller Parathyroid gland Parathyroid hormone PTH Parathormone

  7. http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab24/EXAMPLES/EXPARATH.HTMhttp://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab24/EXAMPLES/EXPARATH.HTM

  8. Ca++ absorption Ca++ reabsorbed Bone resorption Kidney Bone Intestine minutes hours days Response to low Ca++ Blood Ca++ Blood Ca++ Calcium-sensing Receptor in PTH gland PTH Parathyroid gland

  9. 7-pass protein G-protein Coupled receptor GPCR 34

  10. adenylyl cyclase G enzyme phospholipase C 2nd messenger effect 40

  11. Ca++ 115 aa 90 aa (-) 84 aa high Ca++ PTH cell IP3 DAG ER Golgi vesicles

  12. PTH on bone • Increase blood Ca++ • Bone breakdown • Expect receptors on osteoclasts but receptors on osteoblasts

  13. Fast release of calcium Activates calcium channels in osteocytes, so calcium transferred from bone fluid to osteocytes then via gap junctions to osteoblasts to blood.

  14. Slow release of calcium Activates osteoclast proliferation, activity, break down mineralized bone

  15. IP3 cAMP RANK Osteoclast PTH Osteoblast RANKL

  16. IP3 cAMP OPG Osteoprotegerin PTH Osteoblast RANKL

  17. IP3 cAMP Estrogen RANK osteoclast activity PTH Osteoblast + RANKL OPG

  18. PTH on kidney • Increase blood Ca 2+ • Stimulate active transport of Ca 2+ from tubule • Reabsorb 90% w/o PTH, 99% w/PTH • Stimulate PO 4- excretion, so Ca 2+ doesn’t precipitate

  19. PTH on small intestine • No direct effect • Increase blood Ca++ • Stimulate Ca++ absorption indirectly • activate Vitamin D

  20. Egg yolk, fish oil 7-dehydrocholesterol SKIN UV cholecalciferol 1 alpha hydroxylase activates PTH D calcitriol http://uwcme.org/courses/bonephys/opvitD.html

  21. melanocytes http://www.ultranet.com/~jkimball/BiologyPages/M/MSH.html

  22. melanocyte

  23. cytocrine

  24. Vitamin D Receptor COOH NH2 Transcription activation domain DNA binding domain dimerization domain Vitamin D binding domain

  25. Hormone Response Element Gene to be transcribed 17

  26. = Transcription Factor Vit D RE mRNA protein Physiological effect 18

  27. = Transcription Factor Vit D RE mRNA protein calbindin CaBP Physiological effect 18

  28. Ca++ calmodulin Ca++ Na+ Ca++ calbindin Na+ Ca++-ATPase Ca++

  29. Vitamin D effects • Small intestine • Absorb Ca++ • Kidney • Slight reabsorption Ca++ • Bone • Indirect effect – more Ca++ deposited in bone because increased Ca++ in blood • Via Vit D Receptor – move Ca++ out of bone • Increase number of osteoclasts • Increase protein synthesis in osteoblasts • But these effects less obvious

  30. Ca++ PTH cell IP3 DAG

  31. Ca++ PTH gland PTH Ca++ Why do PTH cells have Vit D receptors? (-) kidney Vit D Small intestine

  32. Vitamin D effects • Small intestine • Absorb Ca++ • Kidney • No effect (slight reabsorption) • Bone • Increase responsiveness to PTH • Increase osteoclast production • Parathyroid gland • Decrease PTH synthesis

  33. Eaton’s catalogue, 1919 Rickets… could be prevented http://uwcme.org/courses/bonephys/opmalacia.html http://timelinks.merlin.mb.ca/imagere4/ref1850.htm

  34. C cells

  35. Calcitonin 32 aa From C cells of thyroid gland In response to high blood Ca2+ Lowers blood Ca2+ through effects on • kidney – increase excretion Ca2+ • bone – increase Ca2+ deposit • CT receptors on osteoclasts –> detach from bone • small intestine – slight decrease resorption

  36. Calcitonin function? Needed only occasionally? Prevent sudden increase blood Ca2+ when ingest a lot? Prevent Mom’s Ca2+ getting too high during pregnancy? Not sure

  37. Food Feces Small intestine PTH D CT ECF PTH Cells Bone D CT PTH Nephron Urine

  38. Ca2+ intake Ca2+ absorbed Ca2+ in blood - Osteoblast Osteoclast FALL Ca2+ deposits Bone density Bone breaks Surgery, pneumonia Death Calcitonin Estrogen Alendronate

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