parathyroid hormone

Parathyroid hormone
PDB rendering based on 1bwx.
Available structures
1bwx, 1et1, 1fvy, 1hph, 1hpy, 1zwa, 1zwb, 1zwc, 1zwd, 1zwe, 1zwf, 1zwg
Identifiers
Symbols	PTH;
External IDs	OMIM: 168450 MGI: 97799 HomoloGene: 266
Gene ontology Molecular function • hormone activity Cellular component • extracellular region Biological process • skeletal development • cellular calcium ion homeostasis • G-protein coupled receptor protein signaling pathway • cell-cell signaling • lactation • induction of apoptosis by hormones • bone resorption • cAMP metabolic process
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5741	19226
Ensembl	ENSG00000152266	ENSMUSG00000059077
UniProt	P01270	n/a
RefSeq	NM_000315 (mRNA)	NM_020623 (mRNA)
	NP_000306 (protein)	NP_065648 (protein)
Location	Chr 11: 13.47 - 13.47 Mb	Chr 7: 113.18 - 113.18 Mb
PubMed search	[1]	[2]

Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca²⁺) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body:^[1] PTH half-life is approximately 4 minutes.^[2]

Function

Regulation of serum calcium

Parathyroid hormone regulates serum calcium levels through its effects on the following tissues:^[3]

Calcium regulation in the human body.^[6] The role of parathyroid hormone is shown in blue.

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

Normal total plasma calcium level ranges from 8.5 to 10.2 mg/dL (2.12 mmol/L to 2.55 mmol/L).^[7]

Regulation of serum phosphate

PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney^[5] which means more phosphate is excreted through the urine.

However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, which 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. The end result is a small net drop in the serum concentration of phosphate.

Vitamin D synthesis

PTH increases the activity of 1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol, the active form of vitamin D.

Regulation of PTH secretion

Secretion of parathyroid hormone is chiefly controlled by serum [Ca²⁺] through negative feedback, which is achieved by the activation of calcium-sensing receptors located on parathyroid cells.^[8] Calcium sensing receptors work by activating the phospholipase C pathway,^[9][10] presumably through a G_qα type of G protein, which ultimately increases intracellular concentration of calcium, which triggers vesicle fusion and exocytosis of parathyroid hormone. It also inhibits (not stimulates, as some^[11] sources state) the cAMP dependent pathway.^[10]

Stimulators

• Decreased serum [Ca²⁺].
• Mild decreases in serum [Mg²⁺].
• An increase in serum phosphate (Since increased phosphate will complex with serum calcium to form calcium phosphate, this causes the Ca sensitive receptors (CaSr) to think that serum Ca has decreased, as CaSR do not sense Calcium phosphate, thereby triggering an increase in PTH)

Inhibitors

• Increased serum [Ca²⁺].
• Severe decreases in serum [Mg²⁺], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).^[11]

Clinical significance

• A high level of PTH in the blood is known as hyperparathyroidism.
  • If the cause is in the parathyroid gland it is called primary hyperparathyroidism. The causes are parathyroid adenoma, parathyroid hyperplasia and parathyroid cancer.
  • If the cause is outside the gland, it is known as secondary hyperparathyroidism. This can occur in chronic renal failure. In secondary hyperparathyroidism, serum Calcium levels are decreased, which causes the hypersecretion of PTH from the parathyroid glands. PTH acts on the proximal tubules in the kidney to decrease reabsorption of Phosphate (increasing its excretion in urine, decreasing its serum concentration). NOTE: however, in chronic renal failure, because the kidneys are failing they are unable to excrete phosphate in the urine, so in this case of secondary hyperparathyroidism, serum calcium will be decreased, but serum phosphate will be increased.

• A low level of PTH in the blood is known as hypoparathyroidism. Causes include surgical misadventure (eg inadvertent removal during routine thyroid surgery), autoimmune disorder, and inborn errors of metabolism.

Measurement

PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations.

The average PTH level is 10-60 pg/ml.

See also

• Calcium metabolism
• Disorders of calcium metabolism
• Parathyroid hormone-related protein

References

Further reading

v • d • e PDB Gallery 1bwx: THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-39, NMR, 10 STRUCTURES   1et1: CRYSTAL STRUCTURE OF HUMAN PARATHYROID HORMONE 1-34 AT 0.9 A RESOLUTION   1fvy: SOLUTION STRUCTURE OF THE OSTEOGENIC 1-31 FRAGMENT OF THE HUMAN PARATHYROID HORMONE   1hph: STRUCTURE OF HUMAN PARATHYROID HORMONE 1-37 IN SOLUTION   1hpy: THE SOLUTION STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-34 IN 20% TRIFLUORETHANOL, NMR, 10 STRUCTURES   1zwa: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 1-34, NMR, 10 STRUCTURES   1zwb: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 2-37, NMR, 10 STRUCTURES   1zwc: STRUCTURE OF BOVINE PARATHYROID HORMONE FRAGMENT 1-37, NMR, 10 STRUCTURES   1zwd: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 3-37, NMR, 10 STRUCTURES   1zwe: STRUCTURE OF HUMAN PARATHYROID HORMONE FRAGMENT 4-37, NMR, 10 STRUCTURES   1zwf: STRUCTURE OF N-TERMINAL ACETYLATED HUMAN PARATHYROID HORMONE, NMR, 10 STRUCTURES   1zwg: SUCCINYL HUMAN PARATHYROID HORMONE 4-37, NMR, 10 STRUCTURES