Parathyroid hormone or parathyrin is produced in the parathyroid glands. The hormone plays a significant role in the regulation of calcium and phosphate balance.
What is parathyroid hormone?
Parathyroid hormone (parathyrin, PTH) is a linear polypeptide hormone produced by the parathyroid glands (glandulae parathyreoideae, epithelial corpuscles) and consists of a total of 84 amino acids. In interaction with vitamin D and its direct antagonist (counterpart) calcitonin, which is formed in the thyroid gland, the hormone regulates the calcium and phosphate balance of the human body. In a healthy state, the reference value is about 11 to 67 ng/l in the blood.
Production, formation, and manufacture
Parathyroid hormone is produced and secreted (released) by the parathyroid glands. Parathyroid glands are four small glands, about the size of a lentil, that are located in pairs to the left and right rear of the thyroid gland. In the hormone-producing main cells of the epithelial corpuscles, the peptide hormone is synthesized and, due to the lack of independent excretory ducts, released directly into the blood (endocrine secretion). In this process, the hormone is first formed as a precursor consisting of 115 amino acids (pre-pro-hormone) at the membrane-bound ribosomes. Ribosomes are RNA-rich particles at which protein synthesis takes place in cells. Subsequently, the amino-terminal sequence is cleaved cotranslationally, i.e. during the translation of mRNA into the amino acid sequence. Another precursor of 90 amino acids (pro-parathyroid hormone) is formed, which is processed in the Golgi apparatus (protein-modifying cell organelle) to produce the final parathyroid hormone.
Function, action, and properties
Parathyroid hormone, together with vitamin D (calcitriol) and the thyroid hormone calcitonin, regulates blood calcium and phosphate levels. With the help of specific receptors on the membrane of the parathyroid cells (so-called G-protein-coupled calcium receptors), the calcium level in the blood is determined. A decrease in blood calcium concentration stimulates the formation and secretion of parathyroid hormone in the parathyroid glands, while increased blood calcium inhibits secretion (negative feedback). Accordingly, hypocalcemia (decreased calcium), for example, forms the stimulus for the release of parathyroid hormone. The direct and indirect effects of the hormone cause an increase in the unbound, free calcium concentration in the blood via stimulation of adenylate cyclase (enzyme) in the bones and kidneys. This directly stimulates the osteoclasts of the bones as well as a reabsorption of calcium in the kidneys (reduced excretion via kidneys with urine). In addition, the phosphate concentration in the blood is lowered by increased excretion via kidneys (inhibited reabsorption). To prevent demineralization of the bone, vitamin D or calcitriol synthesis is stimulated in parallel via the phosphate level thus dropped (hypophosphatemia). Calcitriol promotes bone remineralization by increasing calcium absorption in the small intestine. At the same time, the resulting increased calcium concentration in the blood causes an inhibition of parathyroid hormone release. An analogous function is fulfilled by calcitonin, which is secreted when calcium levels rise and promotes calcium incorporation into bone while inhibiting osteoclast activity. Sustained stimulation of osteoclasts results in gradual bone mass loss. Therefore, for example, secondary hyperparathyroidism (overproduction of parathyroid hormone) is associated with senile osteoporosis. Therapeutically, a fragment of parathyroid hormone (from amino acids 1 to 34) is used here as a drug that stimulates bone formation.
Diseases, ailments, and disorders
In general, impairments of parathyroid hormone metabolism are divided into so-called hyperparathyroidisms (hyperfunction of the parathyroid glands) and hypoparathyroidisms (hypofunction of the parathyroid glands). In hyperparathyroidism, increased parathyroid hormone is produced and secreted. The hormone concentration in the blood is increased. If the hyperfunction can be traced back to an impairment of the parathyroid glands themselves, the diagnosis is primary hyperparathyroidism. This is usually caused by benign (hormone-producing parathyroid adenomas), in very rare cases by malignant tumors (parathyroid carcinomas). In addition, hyperthyroidism can occur in connection with kidney, liver or intestinal diseases as well as a vitamin D or.calcium deficiency occur (secondary hyperparathyroidism). A deficiency of vitamin D or calcium leads to a lowered blood calcium level, which in turn stimulates parathyroid hormone synthesis in the parathyroid glands. In the case of a long-term low calcium level, which can also manifest itself, for example, as a result of renal insufficiency (kidney weakness) – the parathyroid glands permanently synthesize increased parathormone. In the long term, this overproduction can cause parathyroid hyperplasia (proliferation of parathyroid gland tissue), which in turn is associated with manifest, primary hyperparathyroidism. In hypoparathyroidism, on the other hand, there is decreased production and release of parathyroid hormone and the parathyroid hormone concentration in the blood is decreased. If the parathyroid glands do not respond with increased parathyroid hormone secretion despite a decreased calcium concentration, this can usually be attributed to a parathyroid dysfunction (primary hypoparathyroidism). Primary hypoparathyroidism is caused in many cases by autoimmune diseases (including sarcoidosis) or partial removal of tissue from the parathyroid glands (removal of the epithelial corpuscles or parathyroidectomy). In some cases, the parathyroid glands are also injured during surgical procedures on the thyroid gland. Progressive (advanced) tumors as well as hyperthyroidism may cause hypercalcemia (permanently elevated calcium levels), which in turn is associated with decreased parathyroid hormone concentrations. Similarly, vitamin D overdose results in decreased release of parathyroid hormone into the blood.
