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SEFA

Table 39-2. Actions of PTH and 1,25-Dihydroxyvitamin D on Ca++

/Pi Homeostasis

Small Intestine Bone KidneyParathyroid

Gland

PTH No direct action Promotesosteoblastic

growth andsurvivalRegulates M-CSF, RANKL,and OPGproduction byosteoblastsChronic highlevels promotenet Ca

++and Pi

release from bone

Stimulates 1-hydroxylase activity

Stimulates Ca

++

reabsorption by thethick ascending limbof Henle's loop andthe distal tubuleInhibits Pireabsorption byproximal nephrons(represses NPT2aexpression)

No direct action

1,25-DihydroxyvitaminD

Increases Ca++

absorption byincreasing TRPVchannels, calbindin-D and PMCAexpressionMarginally increasesPi absorption

Sensitizesosteoblasts toPTHRegulates osteoidproduction andcalcification

Minimal actions onCa

++reabsorption

Promotes Pireabsorption byproximal nephrons(stimulates NPT2aexpression)

Directly inhibitsPTH geneexpressionDirectlystimulatesCaSR geneexpression

Mechanism of Action of PTH in Calcium and Phosphate Metabolism

The level of circulating calcium in the blood is tightly regulated by the action of the parathyroid hormone.

PTH is a hormone synthesized and secreted by the parathyroid glands in response to plasma calcium

levels. Its main function is to maintain the normal calcium, and to a lesser extent phosphate, levels in theblood. The main stimulus for the release of the hormone is low plasma calcium in blood (detected by

CaSR, a receptor in the gland). Upon release, PTH exerts its action in two main organs: the bones and

the kidneys. Since calcium is an important component of the bones, they serve as the largest reservoir of

this mineral in the body which can be utilized when needed. PTH increases bone resorption by

stimulating osteoclastic activity, thereby releasing both calcium and phosphate in the blood. On the other

hand, PTH also increases calcium reabsorption in the kidney, particulary in the thick ascending limb of

the loop of Henle and distal tubule. It does, however, inhibit phosphate ion (Pi) reabsorption in the

proximal tubule. As a result, excretion of calcium decreases while that of phosphate increases. Lastly,

PTH also increases the absorption of calcium in the small intestines indirectly by promoting the

production of the active form of vitamin D. The exact mechanism involves the stimulation of the activity of

the enzyme 1-hydroxylase which catalyzes the hydroxylation of 24, 25-dihydroxyitamin D (calcidiol) from

the liver into 1, 24, 25- trihydroxyvitamin D (calcitriol), which is the most potent form of vitamin D. Calcitriol

then enhances the absorption of calcium, and to a lesser extent phosphate, in the gut. Hence, the three

mechanisms that correct the levels of calcium in the blood involves: bone resorption, renal reabsorption,

and increase intestinal absorption (via vitamin D) all of which is mediated by the parathyroid hormone.

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