see also:

• calcitonin
• vitamin D
• calcium

• PTH is essential for life - excision of parathyroid glands ⇒ hypocalcaemic tetany ⇒ death;

• A linear 84 AA plypeptide (MW 9500) synthesised and secreted by the chief cells of the 4 parathyroid glands:
  • preproPTH (115AA's) converted to proPTH (90AA's) in E.R. then to PTH in Golgi.

• plasma half-life = 20min. Plasma [] 10-55 pg/ml;
• rapidly cleaved by Kupffer cells into:
  • inactive C-term. fragment MW 7000;
  • active N-term. fragment MW 2500 - metab. slowly;

• decreased by increased free plasma [Ca] via a calcium-sensing receptor (CaR) on parathyroid chief cells
• defects in CaR gene are responsible for:
  • familial benign hypocalciuric hypercalcaemia (FBHH):
    • autosomal dominant, asymptomatic disorder
  • neonatal severe hyperparathyroidism (NSHPT) - rare
  • autosomal dominant hypocalcaemic hypercalciuria (ADHH)
  • polymorphisms may affect urinary calcium excretion & possibly bone mass & thus may have causal role in osteoporosis & idiopathic hypercalciuria
• increased by increased plasma [phosphate] as it lowers free plasma [Ca] & [vitamin D];
• decreased by 1,25 dihydroxycholecalciferol via decreased production of preproOPTH;
• decreased by [Mg];
• increased by B-adrenergic discharge & c-AMP;

• binds to cell membrane receptor + Gs ⇒ adenylate cyclase incr. ⇒ cAMP increased;
  • ⇒ mobilisation Ca & P from bone:
  • ⇒ increased permeability for bone fluid Ca in osteocytes/blasts
  • ⇒ flow Ca into cell from bone fluid;
  • ⇒ increased pumping of Ca out of cell into ECF (facilitated by 1,25);
  • ⇒ increased osteoclast activity and numbers;
  • ⇒ increased P renal exretion via decreased P tubule reabsorption (phosphaturic action);
  • ⇒ decr. Ca renal excretion via increased Ca distal tubule reabsorption;
  • ⇒ increased (1,25) levels ⇒ increased Ca absorption from GIT, etc;
  • THUS, ⇒ increased [Ca], decreased [P], decreased bone mineralisation;
• PTH administration makes degenerated vertebral endplates became less porous
• in mice, PTH stimulates bone formation osteoblasts to produce Slit3 that is known to inhibit the growth of nerve fibers and directly inhibited abnormal nerve outgrowth ¹⁾

• hypoparathyroidism:
  • excision of parathyroid glands causes slowly developing hypocalcaemia over days/wks leading to tetany;
• Pseudohypoparathyroidism:
  • [PTH] N or increased
  • due to either:
    • cong. 50% reduction in Gs ⇒ abnormal receptor response;
    • defective phosphaturic response to PTH;
• see also hyperparathyroidism