Parathyroid hormone

Parathyroid hormone (PTH),  is a hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

Gene location Chromosome 11.

PTH influences bone remodeling

Molecular weight of 9500 and contains 84 amino acid residues.

PTH is a polypeptide containing 84 amino acids, which is a prohormone.

It has a molecular mass around 9500 Da.


Two types of PTH receptors exist:


Parathyroid hormone 1 receptors, activated by the 34 N-terminal amino acids of PTH, are present at high levels on the cells of bone and kidney. 


Parathyroid hormone 2 receptors are present at high levels on the cells of central nervous system, pancreas, testes, and placenta.


PTH action is opposed by the hormone calcitonin.


The half-life of PTH is about 4 minutes.


Mean hormone level 7 times normal in patients receiving hemodialysis.

The parathyroid gland releases PTH which maintains calcium in homeostasis.


Parathyroid hormone secretion is determined mainly by serum ionized calcium concentration through negative feedback. 


Normal total plasma calcium level ranges from 8.5 to 10.2 mg/dL.


Parathyroid gland cells express calcium-sensing receptors on the cell surface. 

PTH is secreted when [Ca2+] is decreased, and calcitonin is secreted when serum calcium levels are elevated.


The parathyroid gland regulates calcium that is bound to the extracellular proteins inplasma proteins or to plasma phosphate.

It stimulates bone resorption, and conversion of calcidiol to calcitriol, which increases G.I. calcium absorption.

PTH enhances  kidney calcium resorption, which increases hypercalcemia.

An increase in serum phosphate causes forms calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) triggering an increase in PTH).

A calcium sensing receptor (CaSR) is highly expressed in parathyroid cells and detects changes in ionized calcium.

 A decrease in ionized calcium activates the CaSR and triggers a rapid release of PTH within minutes restoring serum ionized calcium towards baseline.

PTH stimulates osteoclast mediated bone resorption, releasing skeletal calcium into the serum.

PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system.


The G-protein-coupled calcium receptors bind extracellular calcium and may be found on the surface of cells distributed in the brain, heart, skin, stomach, C cells, and other tissues. 


In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C. 


Hydrolization then liberates  intracellular calcium and results in a release of calcium into the cytoplasmic space. 


High cytoplasmic calcium concentration inhibits the fusion of vesicles containing granules of preformed PTH with the membrane of the parathyroid cell, and thus inhibits release of PTH.


Magnesium serves in the parathyroid glands as a stimulus-secretion coupling: A decrease in serum magnesium levels stimulates the reabsorptive activity PTH has on the kidneys. 


Severe hypomagnesemia inhibits PTH secretion and also causes resistance to PTH.


Severe hypomagnesemia leads to a form of hypoparathyroidism that is reversible.


Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine.


PTH enhances the release of calcium from the large reservoir contained in the bones.

Increases bone resorption through increased osteoclastic activity, decreases renal calcium clearance increases renal phosphorus clearance, increases serum 1,25-dihydroxyvitamin D and stimulates intestinal calcium absorption.

Fibroblast growth factor-23 (FGF23) is produced in osteoblasts in response to increases in serum phosphate.


PTH binds to the fibroblast growth factor receptor of the parathyroid and suppresses PTH release. 

Around 250 mmol of calcium ions are filtered into the glomerular filtrate per day: Most of this (245 mmol/d) is reabsorbed from the tubular fluid.


About 5 mmol/d are excreted in the urine. 


This reabsorption of calcium ions occurs throughout the tubule.


Most, 60-70% of calcium ions are reabsorbed in the proximal tubule.


Circulating parathyroid hormone influences the reabsorption only that occurs in the distal tubules and the renal collecting ducts.

More importantly is PTH’s effect on the kidney is its inhibition of the reabsorption of phosphate from the tubular fluid, resulting in a decrease in the plasma phosphate concentration. 

Phosphate ions form water-insoluble salts with calcium.


A decrease in the phosphate concentration of the blood plasma increases the amount of calcium that is ionized.


PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney.


PTH increases phosphate excreted through the urine.


PTH, however, enhances the uptake of phosphate from the intestine and bones into the blood. 


In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. 


The absorption of phosphate is not as dependent on vitamin D as is that of calcium. 


With the breakdown of bone slightly more calcium than phosphate is released from the breakdown of bone. 


Bone remodeling is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time.

PTH is secreted in response to low blood serum calcium levels. 


PTH indirectly stimulates osteoclast activity within the bone matrix, to release more ionic calcium into the blood to elevate a low serum calcium level. 


PTH is secreted primarily by the chief cells of the parathyroid glands. 

PTH indirectly stimulates osteoclasts.

The resulting multinucleated cells are osteoclasts, which ultimately mediate bone resorption.

Bone resorption by destruction of bone by osteoclasts, occurs indirectly as stimulated by PTH. 


Osteoclasts do not have a receptor for PTH, but PTH binds to osteoblasts, the cells responsible for creating bone. 


PTH binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of osteoprotegerin (OPG). 


Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. 


The binding of RANKL to RANK stimulates osteoclast precursors.

PTH acts on bone, the kidneys, and the GI tract to increase calcium reabsorption and phosphate excretion, and stimulates the conversion of Vitamin D to its most active variant, 1,25-dihydroxyvitamin D3, which further stimulates calcium absorption in the GI tract.


PTH activity occurs  via the parathyroid hormone 1 receptor (PTH1) in the kidneys and bones, or via the parathyroid hormone 2 receptor (PTH2) in the central nervous system and brain, as well as the bones and kidneys.

1,25-dihydroxy vitamin D is  the form of vitamin D that is the active hormone which stimulates calcium uptake from the intestine.


Vitamin D activation occurs in the kidney.


PTH effect on the kidney is also the stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. 

Vitamin D activation occurs in the kidney. PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). 

This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin.

PTH stimulates the production of calcitriol.

Estrogen also regulates this pathway through its effects on PTH. 


The main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate, the counter ion of Ca ++.

Daily parathyroid hormone increases central bone mass 8-10 per cent per year for two years of administration.

After treatment some or all of the bone gained during treatment appears to be lost if treatment is not reinstituted.

Disorders of  PTH, such as hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes can cause bone disease, hypocalcemia, and hypercalcemia.

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