PARATHYROID HORMONE:
Parathyroid Gland:
- Sense circulating levels of Ca2+
- Release Ca2+ in response to plasma Ca2+ (therefore, act to increase plasma Ca++)
Structure of PTH:
- Synthesized from a larger molecule (pre-pro PTH)
- Secreted PTH is 84AA long
- N terminus is the functional end of the hormone
o Teriparatide is a drug that mimics this end of the PTH molecule
Used in the treatment of osteoporosis because under some conditions
(sporadic/periodic release) PTH actually promotes bone building
Secretion of PTH:
- Ca2+ sensing receptor on the surface of parathyroid chief cell binds Ca2+ (senses levels in
blood)
- If Ca2+ levels increase:
o Receptor binds Ca2+, activates Gq mechanism of cell signalingactivates
PLCPIP2 IP3+DAG
o IP3 release of Ca2+ from the ER and increase intracellular levels of Ca2+
o This increase in Ca2+ INHIBITS vesicle docking and fusion, and PTH is no
longer released**(PTH synthesis is also inhibited)
o DAG activates PKC and contributes to the same pathway and prevents vesicle
fusion with cell membrane
PTH Action:
- Works to maintain circulating Ca2+levels (increases Ca2+ when low)
- Ca2+PTH release
- Direct effects:
o Bone: bone Ca2+ Resorption
o Kidney:
Kidney Tubule Ca2+ Reabsorption
enzyme for conversion of 25(OH)D3 1,25(OH)2D3 (active vitamin D3)
kidney tubule Pi reabsorption
- Indirect effects: due to Vit D
o Gut:Intestinal Ca2+ Reabsorption from dietary sources
o Bone: bone resorption
o Kidney: ca2+ reabsorption in tubules
VITAMIN D:
Synthesis:
- We can synthesize vitamin D in our skin using UV light
o 7-Dehydrocholesterol + UV Cholecalciferol
o Therefore, not really a vitamin unless there is a lack of UV light and we can no
longer produce it (at which point we would have to obtain it from the diet)
- No endocrine gland that produces it, but has hormone-like properties
- Cholecalciferol 25-(OH)-D3 in liver = Storage form
- 25-(OH)-D3 1,25-(OH)2-D3 (Active form) in kidneythis step is stimulated by PTH
- Vitamin D receptors are located almost everywhere in the body and therefore, their
function is not limited solely to Ca2+ regulation (other functions are not really well
understood)
Effects of Vit D
- Ca2+ & PO43-Absorption in the Gut:
- acts synergistically w/ PTH to Ca2+ reabsorption in kidney
- Directly acts to mobilize Ca2+ out of bone
- Thus overall effect of Ca2+ is bone mineralization
Vit D regulates Ca2+ absorption in the gut
o A direct paracellular path for Ca2+ reabsorption thats not Vit D dependent
o Vit D controlled reabsorption of Ca2+ is under a Vit D receptor control.
Vitamin D acts like a steroid hormone, enters nucleus and alters transcription
of genes, resulting in the production of proteins required for the transport of
Ca2+ out of the gut
Proteins synthesized include:
Ca2+ channel (bring Ca2+ into intestinal cells from lumen)
Calbindin (Ca2+ binding protein that helps create a favorable Ca2+ gradient
allowing more Ca2+ to enter from lumen)
Ca2+ transporter (ATP dependent) to move it to the ISF
Ca2+/Na+ transporter (not ATP dependent)
Regulation of Phosphate Absorption:
o Promotes absorption of phosphate from intestine as well
o Behaves in a similar fashion to above:
o Alters gene transcription resulting in synthesis of proteins associated with
transport of phosphate out of the lumen and into the ISF (one transporter on each
side of the intestinal cell)