Parathyroid hormone

Parathyroid hormone
Ribbon / rod model of amino acids 1-34 of PTH according to PDB  1BWX
Existing structural data : 1bwx , 1et1 , 1fvy , 1hph , 1hpy , 1zwa , 1zwb , 1zwc , 1zwd , 1zwe , 1zwf , 1zwg
Properties of human protein
Mass / length primary structure	84 amino acids
Precursor	(115 amino acids)
Identifier
Gene names	PTH  ;
External IDs	OMIM :  168450 UniProt :  P01270 MGI :  97799
Drug information
ATC code	H05 AA03
Occurrence
Homology family	Parathyroid hormone
Parent taxon	Amniotes
Orthologue
	human	House mouse
Entrez	5741	19226
Ensemble	ENSG00000152266	ENSMUSG00000059077
UniProt	P01270	Q9Z0L6
Refseq (mRNA)	NM_000315	NM_020623
Refseq (protein)	NP_000306	NP_065648
Gene locus	Chr 11: 13.49 - 13.5 Mb	Chr 7: 113.39 - 113.39 Mb
PubMed search	5741	19226

The parathyroid hormone ( PTH , English abbreviation of parathyroid hormone ), and parathyroid hormone or parathyroid hormone , is a peptide hormone consisting of 84 amino acids , which in the main cells of parathyroid gland is formed. The main function of the parathyroid hormone is the maintenance of a sufficient calcium concentration in the blood plasma to maintain calcium homeostasis in the body tissues by means of calcium shift and control of calcium excretion . A decrease in this concentration induces increased PTH secretion. Various causes can be responsible for a too high or too low content of PTH in the blood ( hyperparathyroidism or hypoparathyroidism ). Changes in the PTH gene that lead to hypoparathyroidism are known.

Genetics and Biosynthesis

The parathyroid hormone is encoded by the PTH gene on the 11th human chromosome . This gene contains three exons , but the first one is not translated . Exon 2 codes for a 25 amino acid sequence that is part of the pre-prohormone and for the actual hormone (84 amino acids). Exon 3 codes for six amino acids that are retained in the prohormone and also contains 351 nucleotides that are not expressed. The parathyroid hormone is used as a pre-pro-hormone (115 amino acids) of membrane-bound ribosomes synthesized and co-translationally with elimination of the amino-terminal signal sequence (pre-sequence) is processed , so that pro-parathyroid hormone (90 amino acids) is produced. The finished parathyroid hormone is created through processing in the Golgi apparatus (see translation ).

Dismantling

The parathyroid hormone only has a half-life of a few minutes and is proteolytically broken down both in the epithelial bodies themselves and in the liver and kidneys . Since only a very small proportion of the parathyroid hormone is responsible for biological activity, proteolysis sometimes produces intermediate products that still have biological activity and can be detected in the blood.

Mechanism and control of secretion

The PTH secretion rate is reciprocally regulated depending on the plasma calcium concentration (ionized fraction), i.e. an increase above the normal value inhibits PTH secretion ( negative feedback ). At a concentration of 1 m mol / l ionized plasma calcium, the maximum PTH secretion rate is achieved and at 1.25 mmol / l a minimum secretion rate of 10%. An increase above 1.25 mmol / l therefore does not lead to any further decrease in the PTH secretion rate (basal secretion activity).

The calcium-sensitive receptor discovered in 1993 is responsible for this regulatory mechanism . This is a G-protein- coupled receptor that, when activated by the ligand (high calcium concentration) , sets the inositol phosphate pathway in motion, which leads to an increase in the cytoplasmic inositol triphosphate and diacylglycerol concentration. Inositol triphosphate probably inhibits adenylyl cyclase , so that the cytoplasmic cAMP concentration falls and the secretion of parathyroid hormone falls as a result.

Effects

Induction of osteolysis

→ Main article : "Regulation" in the article bone remodeling

PTH indirectly leads to the maturation and activation of the osteoclasts and thus to a calcium-phosphate mobilization from the bone tissue .

The osteoclasts themselves do not have PTH receptors. When parathyroid hormone binds to the receptors of osteoblasts , the RANK ligand , among other things, is built into the plasma membrane of the osteoblasts. RANKL interacts with RANK , a membrane receptor that is expressed by osteoclasts and, when activated, promotes osteoclastogenesis. However, a negative calcium balance in the bone only occurs with pathologically increased PTH concentrations.

Inhibition of phosphate absorption

PTH inhibited in the kidney , the phosphate reabsorption (recovery) by the proximal tubule cells in the proximal tubule and increases the calcium absorption (recovery) in the distal tubule. Phosphate is primarily transported from the primary urine back to the renal epithelial cells of the proximal tubule via a sodium phosphate co-transporter (NPT2). From there, phosphate returns to the blood. If sufficient phosphate is ingested through food, parathyroid hormone inhibits phosphate uptake in the kidneys.

The inhibition takes place by the fact that the NPT2 co-transporter is internalized under the action of the parathyroid hormone and broken down in lysosomes. This reduces the number of active transport molecules in the luminal cell membrane. This process is the binding of PTH to its receptor PTHR1 and following it, increase in the cytosolic concentration of the second messengers cAMP followed by activation of protein kinase A triggered. Although the binding of PTH to PTHR1 also leads to an activation of protein kinase C via an increase in the IP ₃ concentration , it has been shown that this is of minor importance for the acute regulation of the available NPT2 cotransporters.

So the blood phosphate level drops as more phosphate is excreted in the urine. This makes perfect sense, as it means that more free ionized calcium can be present in the blood again (which, if the phosphate concentration is too high, forms a poorly soluble complex with this in the kidney, which precipitates and leads to the so-called calcified kidney ).

Induction of the biosynthesis of calcitriol

In addition, PTH increases the activity of 1α-hydroxylase , the key enzyme of calcitriol biosynthesis (vitamin D3), which is localized mainly in the kidney, and also the enteral with the aid of (vitamin D3) PTH calcium absorption in the terminal ileum increased .

clinic

Blood value ( reference range ):

• Parathyroid hormone in serum: 12–72 ng / l or 1.5–6.0 pmol / l

Elevated blood values ​​( hyperparathyroidism ):

• Degenerated epithelial cells ( adenomas or, rarely, carcinomas ) are no longer subject to calcium-dependent secretion control. This leads to an uncontrolled increase in the parathyroid hormone level ( primary hyperparathyroidism) and thus to hypercalcemia .
• The body reacts to hypocalcemia as a result of kidney, liver or intestinal diseases with increased secretion of parathyroid hormone ( secondary hyperparathyroidism) due to hyperplasia of the epithelial cells.
• If the cause of secondary hyperparathyroidism is suddenly treated (e.g. kidney transplantation), the basal secretion of parathyroid hormone remains increased due to the reactive epithelial body hyperplasia ( tertiary hyperparathyroidism). The result is hypercalcaemia.
• In the context of malignant diseases ( bronchial carcinoma , breast carcinoma , prostate carcinoma , plasmacytoma ), paraneoplastic hypercalcemia can occur. The degenerated cells form a peptide (PTHrP) related to parathyroid hormone, which acts like parathyroid hormone ( pseudohyperparathyroidism ).

Low blood values ​​( hypoparathyroidism ):

• After thyroid surgery, epithelial adenoma removal or autoimmune, the lack of functional parathyroid tissue can lead to a parathyroid hormone deficiency. The calcium level falls and as a result, if the missing hormone or calcium is not replaced, muscle cramps (hypocalcemic tetany) up to severe seizures and death. The constellation of hypocalcaemia , hypomagnesaemia and hyperphosphataemia with normal kidney function ( creatinine level ) and the exclusion of malassimilation ( albumin level ) indicate a functional disorder of the epithelial cells. A low blood level of parathyroid hormone proves the diagnosis of hypoparathyroidism.

Individual evidence

1. ↑ UniProt P01270
2. ↑ Parathyroid hormone.  In: Online Mendelian Inheritance in Man . (English)
3. Jump up ↑ S. Nagai, M. Okazaki, H. Segawa, C. Bergwitz, T. Dean, JJ Potts, M. Mahon, TJ Gardella, H. Jueppner: Acute down-regulation of sodium-dependent phosphate transporter NPT2a involves predominantly the cAMP / PKA pathway as revealed by signaling-selective parathyroid hormone analogs . In: The Journal of Biological Chemistry . tape 286 , no. 2 , January 14, 2010, p. 1618-1626 , PMID 21047792 .

literature

• Rainer Klinke , Stefan Silbernagl (Ed.): Textbook of Physiology. 4th, corrected edition. Georg Thieme Verlag, Stuttgart 2003, ISBN 3-13-796004-5 .
• Attila Fonyó (Ed.): Principles of Medical Physiology. 1st edition. Medicina Publishing House, Budapest 2002, ISBN 963-242-726-2 . (English)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !