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

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

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

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

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

11. http://education. vetmed. vt

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

13. 7-pass protein G-protein Coupled receptor GPCR34 34

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

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

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

17. 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.

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

19. PTH
Osteoblast
IP3
cAMP
Osteoclast
RANKL
RANK

20. PTH
Osteoblast
IP3
cAMP
RANKL
OPG
Osteoprotegerin

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

22. 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

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

24. Egg yolk, fish oil 1 alpha hydroxylase PTH 7-dehydrocholesterol UV
SKIN UV
cholecalciferol
1 alpha hydroxylase
activates
PTH D
calcitriol

27. melanocytes

28. melanocyte

29. cytocrine

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

32. Hormone
Response
Element
Gene to be
transcribed 17 17

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

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

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

36. Vitamin D effects Small intestine Kidney Bone Absorb Ca++
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

37. Ca++
PTH cell
IP3
DAG

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

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

40. Rickets… could be prevented
Eaton’s catalogue, 1919

41. C cells

42. 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

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

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

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