What is the function of parathyroid hormone (PTH) in the body?

Parathyroid Hormone Function

Parathyroid hormone (PTH) is the primary regulator of calcium homeostasis, acting through three main mechanisms: increasing calcium release from bone, enhancing renal calcium reabsorption while decreasing phosphate reabsorption, and stimulating vitamin D activation to increase intestinal calcium absorption. 1

Primary Physiological Actions

Calcium Regulation

• PTH is released from the parathyroid glands in response to hypocalcemia, detected via calcium-sensing receptors on the parathyroid glands 1
• The hormone increases serum calcium through coordinated actions on three target organs: bone, kidney, and intestine (indirectly) 1, 2

Renal Effects

• In the distal and proximal renal tubules, PTH binding to PTH1R increases calcium reabsorption while simultaneously decreasing phosphate reabsorption, leading to phosphaturia 1, 3
• This phosphaturic effect is particularly critical in chronic kidney disease as a compensatory mechanism to maintain normal serum phosphate levels 3
• PTH stimulates the enzyme 1-α-hydroxylase (CYP27B1) in the kidney to convert 25-hydroxyvitamin D into the active form 1,25-dihydroxyvitamin D 1

Bone Effects

• PTH binding to PTH1R in bone stimulates the release of both calcium and phosphate from bone into circulation 1
• PTH directly stimulates osteoblasts and osteocytes, which then activate osteoclasts through the RANK/RANK-ligand system, promoting bone remodeling 4
• The net effect on bone mass depends critically on the pattern of PTH exposure: intermittent administration favors bone formation, while continuous elevation promotes bone resorption 4

Intestinal Effects (Indirect)

• PTH increases intestinal calcium absorption indirectly by stimulating production of 1,25-dihydroxyvitamin D, which then acts on the intestine to enhance calcium absorption 1, 5

Molecular Structure and Activity

Hormone Structure

• PTH is synthesized as a 115-amino acid precursor (pre-proPTH) in the chief cells of the parathyroid glands, which is cleaved to proPTH and then to the biologically active 84-amino acid peptide 1
• The N-terminal region (amino acids 1-34) contains the biologically active portion sufficient for mineral ion homeostasis 5, 6
• The first 7 amino acids of the N-terminal region are critical for biological function 3

Receptor Interactions

• PTH exerts its effects through binding to the PTH1 receptor (PTH1R), which is part of the type II G-protein-coupled receptor family 1, 7
• PTH1R signaling operates through calcium mobilization, cAMP generation, and protein kinase C (PKC) activation 8

Integrated Hormonal System

Interaction with Other Hormones

• PTH functions as part of a complex regulatory system involving three central hormones: PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23 (FGF23) 1, 3
• FGF23 is released in response to high concentrations of phosphate, PTH, and 1,25-dihydroxyvitamin D, and acts to increase phosphate excretion and inhibit vitamin D activation 1
• The overall result of PTH action is increased calcium concentration without affecting net phosphate concentration, as phosphate released from bone is excreted by the kidneys 1

Clinical Significance

Measurement Considerations

• PTH is measured by immunoassay methods of different generations that vary in their detection of PTH fragments and isoforms in addition to biologically active PTH 1
• Second-generation "intact PTH" assays overestimate biologically active PTH by detecting inactive fragments, particularly the 7-84 PTH fragment 3
• Third-generation assays are more specific, measuring only full-length 1-84 PTH by using antibodies directed against the first four amino acids 3
• Lack of standardization leads to remarkable differences in PTH concentrations measured between different laboratories, even when using the same assay generation 1

Pathophysiological States

• Dysregulation of PTH occurs in hyperparathyroidism (excessive PTH) and hypoparathyroidism (insufficient PTH), leading to significant clinical complications in calcium and bone metabolism 6, 4
• In chronic kidney disease, PTH levels rise when GFR falls below 60 mL/min/1.73 m² as a compensatory response to maintain mineral homeostasis 3

Additional Target Organs

• Beyond the classical target organs, the pancreas is a direct target for PTH, with both endocrine and exocrine pancreatic cells expressing PTH receptors that mediate effects on insulin secretion and pancreatic juice production 8
• PTH-related peptides and receptors are expressed throughout the central nervous system, where they may exert protective effects against neuroinflammation and neurodegeneration 7