Parathyroid hormone (PTH), also known as parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands. It plays a critical role in regulating serum calcium and phosphate levels through its actions on bone, kidneys, and the small intestine. PTH increases serum calcium levels and is opposed by calcitonin. It also promotes the synthesis of calcitriol, the active form of vitamin D.

PTH is secreted in response to low blood serum calcium (Ca²⁺) levels and is a key regulator of bone remodeling, the continuous process of bone resorption and formation. PTH indirectly stimulates osteoclast activity, promoting the release of calcium from the bone matrix to restore serum calcium levels. The bones serve as a reservoir of calcium, releasing it as needed to maintain homeostasis in the face of fluctuating metabolism, stress, and nutritional status.

Produced primarily by the chief cells of the parathyroid glands, PTH is a polypeptide prohormone consisting of 84 amino acids and has a molecular mass of approximately 9500 Da. Its gene is located on chromosome 11.

PTH exerts its biological effects via two main receptors. The Parathyroid hormone 1 receptor, activated by the 34 N-terminal amino acids of PTH, is highly expressed in bone and kidney cells. The Parathyroid hormone 2 receptor is predominantly found in the central nervous system, pancreas, testes, and placenta. The hormone has a short half-life of approximately 4 minutes. Dysregulation of PTH secretion, as seen in conditions like hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes, can result in bone disease, hypocalcemia, or hypercalcemia.

hPTH-(1-84) crystallizes as a slightly bent, long, helical dimer. The extended helical conformation of hPTH-(1-84) is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 Å resolution.

Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine:

In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of osteoprotegerin (OPG). Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a monocyte lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate bone resorption. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism.

In the kidney, around 250 mmol of calcium ions are filtered into the glomerular filtrate per day. Most of this (245 mmol/d) is reabsorbed from the tubular fluid, leaving about 5 mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60–70%, of it in the proximal tubule), except in the thin segment of the loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the distal tubules and the renal collecting ducts (but see Footnote). A more important effect of PTH on the kidney is, however, its inhibition of the reabsorption of phosphate (HPO₄²⁻) from the tubular fluid, resulting in a decrease in the plasma phosphate concentration. Phosphate ions form water-insoluble salts with calcium. Thus, a decrease in the phosphate concentration of the blood plasma (for a given total calcium concentration) increases the amount of calcium that is ionized. A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.