PARATHROMONE

PARATHORMONE/PARATHYROID HORMONE/PTH

• Synthesized by principal/chief cells of parathyroid gland.

Major role:

• Increases bone remodelling:

– By directly stimulating osteoblasts

– Indirectly stimulating osteoclasts via osteoclast-stimulating factor 

– Since Osteoclasts do not have any PTH receptors

REGULATION OF SECRETION:

• Mainly depend on Plasma Ca⁺² concentration

• Second messenger – cAMP

PTH secretion increased:

• Decreased serum Ca⁺² concentration.

• Hyperphosphatemia

• Mild decreases in serum Mg²⁺

PTH secretion decreased:

• Increased serum Ca⁺² concentration. 

• Severe decreases in serum Mg²⁺

• Calcitriol

RECEPTORS

Type 1:

• PTH 1R (h-PTH/ Parathyroid Hormone-related Protein PTH-rP)

• Bone (osteoblast) & kidney

• 2nd messenger – cAMP (main), IP3 & calcium.

Type 2:

• PTH 2R (h-PTH2)

• Brain, placenta, pancreas & testis.

• 2nd messenger – cAMP

Type 3:

• CPTH / Carboxyl-terminal PTH fragments

• Osteocyte

Note: 

• PTH receptor is not present in intestine.

– Hence, indirect PTH action (via Vitamin D3).

• PTH-rP can bind to PTH receptor & mimic its actions.

– PTH-rP is major cause of hypercalcemia in cancer

RELATIONSHIP BETWEEN CALCIUM & PTH:

• PTH raises plasma Ca⁺² in three ways.

• Mobilizes bone  Ca⁺² 

– By increasing bone resorption.

• Increases gastrointestinal absorption of Ca⁺² indirectly.

– By increasing renal synthesis of 1,25 dihydroxy D₃ calcitriol.

• Increases Ca⁺² reabsorption in distal tubules of kidney.

RELATIONSHIP BETWEEN PHOSPHATE & PTH:

• Decreases phosphate reabsorption from proximal tubules of kidney.

ACTIONS:

ON BONE:

• Fastest action is on bone.

• PTH increases bone resorption 

• Brings both Ca2+ & phosphate from bone mineral into ECF

• increased hydroxyproline excretion is sign of bone resorption.

Mechanism of action:

• PTH receptors located on osteoblasts & not on osteoclasts.

Step 1: Initial & fast action:

• Increases bone formation by direct action on osteoblasts.

• Basis for intermittent PTH administration in osteoporosis treatment.

Step 2: Long-lasting action:

• Indirect action on osteoclasts

• Increases bone resorption

• Mediated by cytokines released from osteoblasts.

• Thus, osteoblasts required for bone-resorbing action of PTH on osteoclasts.

ON KIDNEY:

• Major regulating factor for calcium reabsorption.

On Proximal convoluted tubule:

• “Phosphaturic effect” – Inhibits renal phosphate reabsorption

• Increased urinary cAMP.

• cAMP – 2nd messenger of PTH.

• Production of 1,25-dihydroxycholecalciferol (Calcitriol).;

On Distal convoluted tubule:

• Increases renal Ca^₂₊ reabsorption

ON INTESTINE:

• No direct effect on calcium absorption.

• Indirect increases Ca²⁺ absorption 

• Activating 1- alpha-hydroxylase, resulting in calcitriol formation.