Skeleton and metabolism Flashcards
Hormones with skeletal effects
- Oestrogen
- Androgens
- Cortisol
- Parathyroid hormone (PTH)
- Vitamin D (calcitriol)
- Calcitonin
Hormones secreted from the skeleton
• FGF-23 (fibroblast growth factor 23)
Bone as a metabolic organ
Bone turnover serves homeostasis of serum calcium, phosphate, in conjunction with • Parathyroid hormone (PTH) • Vitamin D (1,25-dihydroxy D3) • Calcitonin • FGF-23
Daily calcium turnover
Daily intake recommended 1000-1200mg (25-30 mmol)
Extracellular: plasma Ca 2.2-2.6 mmol L-1
About half is free [Ca2+] (physiologically active), half protein bound (mainly albumin)
AW Ca = 40, 40 mg = 1 mmol. 900/40 = 22.5 mmol in ECF.
Parathyroid glands
- PTH synthesised by parathyroid chief cells
- Secreted as 84 AA polypeptide
- Short half-life in circulation (<5 min)
- Parathyriod. 80K cells continuously monitoring blood Ca, and increasing or decreasing PTH secretion accordingly.
Parathyroid hormone (PTH)
- Major role is defence against hypocalcaemia
- Plasma Ca is maintained 2.2 – 2.6 mM (free, ionized Ca2+ is approximately half)
- Free Ca sensed by GPCR on chief cells
- Ca binding supresses PTH release
Vitamin D
- Calcitriol (really a steroid hormone, not a vitamin!)
- Synthesised in skin in response to exposure to UV (‘sunshine vitamin’)
- Activated by 2 metabolic steps
Actions of PTH
Site of regulation is chief cells of PT gland
• Secretion increases as plasma [Ca2+] decreases
Actions:
• Promotes release of Ca from bone
• Increases renal Ca reabsorption
• Increases renal Pi excretion
• Upregulates 1α hydroxylase activity
Actions of calcitriol
Site of regulation is control of 1α hydroxylase in kidney
Increased by
• PTH
• Low phosphate
Actions:
• Increase absorption of Ca and Pi from GI tract
Little absorption in absence
• Inhibits PTH secretion (transcription)
• Complex effects on bone, generally in synergy with PTH
• The only way to increase the body’s Ca reservoir is via absorption from the gut, and little takes place in the absence of vitamin D.
Calcium homeostasis
- 99% of body calcium is in bone
- Remaining 1% is mainly intracellular
- Hormonal control of the tiny (<0.1%) extracellular fraction is what maintains Ca balance
Actions of PTH on bone
• PTH receptors on osteoblasts and osteoclasts
• Promotes bone formation
• Activates osteoclasts via RANKL
• Promotes bone remodelling
Effect depends on concentration dynamics
• Intermittent low doses are anabolic
• Persistent high concentration leads to excess resorption over formation – bone loss
Lacunar-Canalicular network
• Allows communication between osteocytes and from osteocytes to surface cells and systemic circulation
FGF-23: a hormone secreted by osteocytes
- Hypophosphatemic rickets: rare phosphate-wasting conditions leading to bone mineralization defects (osteomalacia)
- Consortium investigating autosomal-dominant HR (ADHR) traced mutation in gene that turned out to be FGF-23
Actions of FGF-23
- Expressed and secreted by osteocytes
- Increases renal Pi excretion (by reducing Na-Pi reabsorption from proximal tubule)
- Increased by calcitriol and Pi
- Inhibits calcitriol synthesis
Disorders of calcium
- Normal range 2.2 – 2.6 mM
- Hypocalcaemia
- Hypercalcaemia