Parathyroid hormone (PTH)
Also known as: PTH, parathormone, parathyrin
An 84-amino-acid peptide from parathyroid chief cells that raises plasma calcium within minutes by acting on kidney and bone and by stimulating calcitriol synthesis, while lowering plasma phosphate.
Overview
PTH is the principal minute-to-minute regulator of ionised calcium. Chief cells store preformed PTH and release it within seconds when the calcium-sensing receptor detects a fall in Ca²⁺; the N-terminal (1–34) region carries full biological activity. PTH binds the PTH1 receptor, a GPCR coupled to Gs (cAMP) and Gq (IP₃/Ca²⁺), on renal tubular cells and osteoblasts.
Kidney: increases Ca²⁺ reabsorption in the distal convoluted tubule (TRPV5 channels); inhibits phosphate reabsorption in the proximal tubule by internalising NaPi-IIa cotransporters (phosphaturia) — so the Ca × P product does not rise and calcium phosphate does not precipitate; stimulates proximal 1α-hydroxylase, producing calcitriol. Bone: osteoblasts respond by expressing RANKL and reducing osteoprotegerin, which activates osteoclasts and releases Ca²⁺ and phosphate — the effect of continuous high PTH. Intermittent PTH, by contrast, is anabolic, increasing bone formation. Gut: indirect, via calcitriol.
- Location
Source: chief cells of the parathyroid glands. Targets: kidney (proximal and distal tubules), bone (osteoblasts → osteoclasts); gut indirectly.
Function
- Raises plasma ionised calcium.
- Lowers plasma phosphate (phosphaturia).
- Stimulates calcitriol synthesis (increasing intestinal Ca²⁺ absorption).
- Regulates bone remodelling (catabolic when continuous, anabolic when intermittent).
- Physiology
Class: peptide (84 aa). Receptor: PTH1R — Gs/cAMP and Gq/IP₃. Half-life ≈2–4 min. Reference ≈1.6–6.9 pmol/L (≈15–65 pg/mL).
- Regulation
Low ionised Ca²⁺ (CaSR) stimulates release (steep sigmoidal relationship); high Ca²⁺ and calcitriol inhibit secretion and synthesis; hyperphosphataemia stimulates; FGF-23 inhibits; magnesium is required (severe hypomagnesaemia blocks release and causes PTH resistance).
Clinical significance
Hyper- and hypoparathyroidism
Primary hyperparathyroidism (adenoma) causes hypercalcaemia with low phosphate; secondary (CKD, vitamin D deficiency) and tertiary forms follow chronic hypocalcaemia. Hypoparathyroidism (post-surgical, autoimmune, DiGeorge) causes hypocalcaemia with high phosphate and tetany.
PTH-related peptide (PTHrP)
Secreted by squamous-cell carcinomas (lung, head and neck), breast and renal cancers; it activates PTH1R and causes humoral hypercalcaemia of malignancy with suppressed PTH.
Pseudohypoparathyroidism
End-organ resistance (GNAS mutation affecting Gsα): hypocalcaemia and hyperphosphataemia with high PTH; type 1a has Albright hereditary osteodystrophy (short stature, round face, short 4th/5th metacarpals).
Teriparatide
Daily injections of PTH 1–34 stimulate bone formation in severe osteoporosis.
Mnemonics
PTH in the kidney
PTH = Phosphate Trashing Hormone: it dumps phosphate in the proximal tubule while saving calcium distally.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.