Parathyroid hormone, parathormone or parathyrin, is secreted by the chief cells of the parathyroid
glands as a polypeptide containing 84 amino acids. It acts to increase the concentration
of calcium in the blood, whereas calcitonin of the thyroid gland) acts to decrease calcium
concentration. PTH acts to increase the concentration of calcium in the blood by acting upon the
parathyroid hormone 1 receptor and the parathyroid hormone 2 receptor. PTH half-life is approximately
4 minutes. It has a molecular mass of 9.4 kDa.
Structure hPTH-(1-34) crystallizes as a slightly bent,
long helical dimer. Analysis reveals that the extended helical conformation of hPTH-(1-34)
is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone
has been crystallized and the structure has been refined to 0.9 Å resolution.
Function Regulation of serum calcium
Parathyroid hormone regulates serum calcium through its effects on the following tissues:
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. Regulation of serum phosphate
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, 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, 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. The end result of PTH release 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.
Interactive pathway map Click on genes, proteins and metabolites below
to link to respective articles.
Regulation of PTH secretion Secretion of parathyroid hormone is controlled
chiefly by serum [Ca2+] through negative feedback. Calcium-sensing receptors located on parathyroid
cells are activated when [Ca2+] is elevated. The G-protein coupled calcium receptors bind
extracellular calcium and may be found on the surface on a wide variety 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. This hydrolyzes phosphatidylinositol 4,5-bisphosphate
to liberate intracellular messengers IP3 and diacylglycerol. Ultimately, these two messengers
result in a release of calcium from intracellular stores and a subsequent flux of extracellular
calcium into the cytoplasmic space. The effect of this signaling of high extracellular calcium
results in an intracellular calcium concentration that inhibits the secretion of preformed PTH
from storage granules in the parathyroid gland. In contrast to the mechanism that most secretory
cells use, calcium inhibits vesicle fusion and release of PTH.
In the parathyroids, magnesium serves this role in stimulus-secretion coupling. Hypomagnesemia
inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism
that is reversible. Hypermagnesemia also results in inhibition of PTH secretion.
Stimulators Decreased serum [Ca2+].
Mild decreases in serum [Mg2+]. An increase in serum phosphate that do not
sense calcium phosphate, triggering an increase in PTH).
Inhibitors Increased serum [Ca2+].
Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism.
Calcitriol Clinical significance
Hyperparathyroidism, the presence of excessive amounts of parathyroid hormone in the blood,
occurs in two very distinct sets of circumstances. Primary hyperparathyroidism is due to autonomous,
abnormal hypersecretion of PTH from the parathyroid gland, while secondary hyperparathyroidism
is an appropriately high PTH level seen as a physiological response to hypocalcaemia.
A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due
to damage to or removal of parathyroid glands during thyroid surgery.
There are a number of rare but well-described genetic conditions affecting parathyroid hormone
metabolism, including pseudohypoparathyroidism, familial hypocalciuric hypercalcaemia, and
autosomal dominant hypercalciuric hypocalcaemia. In osteoporotic women, administration of an
exogenous parathyroid hormone analogue superimposed on estrogen therapy produced increases in
bone mass and reduced vertebral and nonvertebral fractures by 45 to 65%.
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 8–51 pg/ml. See also
Bone Medical is researching oral delivery methods to assist in treatments.
Calcium metabolism Disorders of calcium metabolism
Parathyroid hormone family Parathyroid hormone-related protein
References
Further reading
External links PTH at Lab Tests Online
Parathyroid hormone: analyte monograph - the Association for Clinical Biochemistry and
Laboratory Medicine Parathyroid Function Test Online