Parathyroid Hormone

Location of the parathyroid glands. Source: Cancer.gov

Other Names

• PTH
• Parathormone
• Parathyrin

Description

PTH is synthesized as a long (115 amino acid) polypeptide known as a prohormone—specifically, preproparathyroid hormone. The long peptide chain is soon cut and rearranged to give a shorter (90 residue) polypeptide, proparathyroid hormone. Further processing leads to the 84-residue hormone, which is stored in cells of the parathyroid gland until needed.

Role of Parathyroid Hormone in the Body

PTH's main role in the body is to ensure that the blood has a constant level of calcium; it has effects on several organs to change the rate of calcium entering and leaving the blood. The effect of PTH on bone is to increase overall transfer of calcium from the mineralized bone matrix to the extracellular fluid (bone resorption), a process that leads to less well-mineralized (and structurally weaker) bone. PTH also acts on the kidney to lower the amount of calcium lost in the urine—that is, PTH increases the efficiency of calcium reabsorption. PTH also promotes the loss of phosphate in the urine and stimulates the activation of vitamin D. The active form of vitamin D, calcitriol, works in the gut to promote the absorption of dietary calcium into the blood.

How It Works

Like other hormones, PTH works by binding to specific receptor molecules on the surface of cells where it is destined to have an effect. The PTH receptor straddles the cell membrane: the external portion recognizes PTH and changes its conformation to relay the binding event to the internal portion of the receptor. The PTH receptor belongs to a large family lf G protein-coupled receptors that span the membrane 7 times and interact with G proteins in the cell.^[1]

Diseases of Parathyroid Hormone

Excessive PTH levels (hyperparathyroidism) results in inappropriately high levels of PTH and predictably high levels of calcium in the blood (hypercalcemia).^[2] The condition is sometimes diagnosed after noting high calcium levels in the blood; there may be no symptoms. If there are symptoms, they may include weakness, anorexia, or anxiety. The cause may be overgrowth of parathyroid tissue in the form of an adenoma (abnormal growth) in one of the four glands. In these cases, removal of the abnormal gland leaves the patient with enough remaining (normal) parathyroid tissue to avoid the need for PTH replacement.

Not enough PTH (hypoparathyroidism) results in too much calcium being lost in the urine and not enough calcium being absorbed from the skeleton or the diet; the result is low blood calcium levels (hypocalcemia).^[3] The related condition of pseudohypoparathyroidism is characterized by normal (or elevated) PTH levels in the face of resistance to the effects of PTH. In either case, blood calcium levels are low and blood phosphate levels are inappropriately high (hyperphosphatemia). Symptoms include nervous hyperexcitability, with paresthesia (abnormal sensation), cramps, tetany, or, in severe cases, convulsions. Treatment consists of oral calcium supplementation and administration of vtamin D to improve calcium absorption from the gut. Hypoparathyroidism may result from removal or destruction of the parathyroid glands or from several rare inherited conditions.

History

In 1909, MacCallum and Voegtlin^[4] noted that removal of the parathyroid glands quickly resulted in rapidly falling blood calcium levels. Subsequent work in the 1920s to purify the hormone established its role in preventing low blood calcium and in raising the calcium level in normal animals^[5]

References

1. ↑ Pioszak AA, Xu HE. Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5034-9. Abstract | Full Text | PDF
2. ↑ Taniegra ED. Hyperparathyroidism. Am Fam Physician. 2004 Jan 15;69(2):333-9. Abstract | Full Text | PDF
3. ↑ Maeda SS, Fortes EM, Oliveira UM, Borba VC, Lazaretti-Castro M. Hypoparathyroidism and pseudohypoparathyroidism. Arq Bras Endocrinol Metabol. 2006 Aug;50(4):664-73. Abstract | Full Text | PDF
4. ↑ MacCallum SG, Voegtlin C. On the relation of tetany to the parathyroid glands and to calcium metabolism. J Exp Med 1909 11:118-151
5. ↑ Rowlands BC. Hyperparathyroidism: an early historical survey. Ann R Coll Surg Engl. 1972 Aug;51(2):81-90. Citation | PDF