Parathyroid hormone

[Ref: AV6:chp10; WG21:chp21]

• Synthesized by chief cells in parathyroid gland

NB:

• Oxyphil cells in parathyroid gland
  = unknown function
  * ? generate chief cells

 

Metablism

Halflife < 10 minutes

Metabolized in liver, then excreted in kidney

 

Actions

• Increase [Ca2+]
  * Act on bones to increase bone resorption (by stimulating osteoclasts via osteoblasts)
  * Act on kidney to increase Ca2+ resorption (by increasing apical calcium channel in DCT)
• Phosphate excretion
  * Act on kidney to decrease PO4 resorption in proximal tubule
• Increase formation of 1,25-dihydroxycholecalciferol

In the long term

• Stimulate both osteoblasts and osteoclasts
  * At mildly elevated PTH level, increase bone growth

NB:

• PTH is elevated
  --> Increased plasma [Ca2+]
  --> Increased filtered load
• Even though Ca2+ resorption is increased in kidney
  --> Urinary excretion of Ca2+ may actually increase overall
  --> May offset a large portion of [Ca2+] increase

Receptors

3 different receptors

G-protein linked

Factors affecting PTH secretion

Factors increasing secretion

• Decreased [Ca2+]
  --> Decreased tonic inhibition on PTH
  --> Increase PTH
  * Ca2+ acts directly on parathyroid gland via cell membrane Ca2+ receptor
  * Negative feedback
  * Main regulatory factor
• 1,25-Dihydroxycholecalciferol
  * Directly inhibit PTH

Factors inhibiting secretion

• High phosphate level
  * To increase excretion by stimulating capacity of parathyroid gland to secrete PTH

NB:

• Magnesium is needed for normal PTH secretion
  * Permissive [WG21:p395]
  * Low magnesium can lead to low PTH and thus low [Ca2+]
• Calcitriol has slower inhibitory effect on PTH

Other notes

• Low PTH leads to hypocalcemic tetany
  * Phosphate may or may not increase
• Parathyroid-related protein (PTHrP)
  * Binds to one of the PTH receptors as well
  * Increase [Ca2+]
  * Marked effect on growth and cartilage development in utero
  * Responsible for 80% of the hypercalcemia of malignancy