Parathyroid hormone
Hormone · 84 amino acids PTH1R, Gs-cAMP t1/2 ~4 min
An 84-amino-acid peptide from the chief cells with a half-life of only about four minutes, acting through the Gs-coupled PTH1R on bone and kidney. Its net effect is to raise serum calcium and lower serum phosphate.
Traced from the start
Detail
- Structure
- 84 amino acids; biological activity resides in residues 1-34, the fragment marketed as teriparatide; half-life 2-4 minutes, cleared by liver and kidney
- Receptor
- PTH1R, the shared PTH/PTHrP receptor, Gs-coupled to adenylyl cyclase and cAMP-PKA, on osteoblasts, osteocytes and the renal tubule
- Four actions
- Bone resorption (indirectly, through osteoblast RANKL), distal tubular calcium reabsorption, proximal tubular phosphate wasting, and stimulation of the renal 1-alpha-hydroxylase
- Net biochemistry
- Serum calcium up, serum phosphate down, urinary phosphate up, urinary cAMP up, calcitriol up
- Suppressed by
- Hypercalcaemia through the calcium-sensing receptor, calcitriol acting on the PTH gene, FGF23, and severe hypomagnesaemia
When it goes wrong
Parathyroid adenoma (about 85% of primary hyperparathyroidism), four-gland hyperplasia (10-15%, MEN 1 and MEN 2A) or carcinoma (under 1%)
Hypercalcaemia with a PTH that is raised or inappropriately inside the reference range; the short half-life is what makes intraoperative PTH monitoring work, a fall of more than 50% at ten minutes predicting cure
Severe hypomagnesaemia from proton pump inhibitors, alcohol, diuretics or cisplatin
Both PTH secretion and PTH action fail: hypocalcaemia that stays refractory to calcium replacement until magnesium is restored
Intermittent daily teriparatide compared with continuous PTH excess
Intermittent exposure is anabolic and builds trabecular bone; continuous exposure is catabolic and drives resorption
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