General scheme of calcium and phosphate metabolism regulation
The concentration of calcium and phosphates in the extracellular fluid is maintained by three hormones: parathyroid hormone, calcitriol, and calcitonin. Parathyroid hormone and calcitriol increase the calcium level in the intercellular fluid, whereas calcitonin decreases it. The coordinated work of these regulators ensures the stability of the plasma Ca²⁺ concentration (norm 2.2–2.6 mmol/L), which is essential for muscle contraction, nerve conduction, blood clotting, and bone tissue mineralization.
Parathyroid hormone: synthesis and secretion stimuli
Parathyroid hormone (PTH) is a polypeptide hormone synthesized by the chief cells of the parathyroid glands. The stimulus for its secretion is a decrease in ionized calcium concentration in extracellular fluid (a subthreshold level). Mnemonic: Parathyroid hormone — parathyroid gland — plasma calcium below threshold.
The main target organs of parathyroid hormone are bones and kidneys; additionally, it indirectly affects the intestine by activating calcitriol synthesis.
Effects of parathyroid hormone on bones and kidneys
In bone tissue, PTH acts via the adenylate cyclase system. Receptors for the hormone are located on osteoblasts; activated osteoblasts release factors that stimulate osteoclasts. Osteoclasts provide bone matrix resorption, resulting in the transfer of calcium and phosphates from the bone into the intercellular fluid.
In the kidneys, parathyroid hormone exerts multidirectional effects on minerals:
- increases calcium reabsorption in the distal tubules;
- decreases phosphate reabsorption, increasing their urinary excretion;
- activates the enzyme 1α-hydroxylase, accelerating calcitriol synthesis.
The separate regulation of Ca²⁺ and phosphates has chemical rationale: if both ions increased simultaneously, they would form insoluble calcium phosphate, and the hormone's effect on ionized calcium would be lost.
Calcitriol biosynthesis
Calcitriol is a steroid hormone, the active form of vitamin D. Its precursor is cholesterol, which is converted into 7-dehydrocholesterol. Further stages of biosynthesis:
- In the skin under the influence of ultraviolet light, 7-dehydrocholesterol is non-enzymatically converted into cholecalciferol (vitamin D₃). The term "vitamin" is historically conditional: a significant part of the compound is synthesized in the body, and only a portion comes from food.
- In the liver, the enzyme 25-hydroxylase converts cholecalciferol into calcidiol (25-OH-D₃), the main transport form.
- In the kidneys, under the action of 1α-hydroxylase, calcidiol is converted into calcitriol (1,25-(OH)₂-D₃), the biologically active form.
The renal reaction itself is regulatory. Activators of 1α-hydroxylase: parathyroid hormone and a decrease in calcium levels. Inhibitors: high calcium concentrations and calcitriol itself (negative feedback).
Calcitonin: antagonist of parathyroid hormone
Calcitonin is a polypeptide consisting of 32 amino acid residues with a single disulfide bond. It is synthesized by parafollicular C-cells (C-cells) of the thyroid gland. The secretion stimulus is an increase in blood calcium concentration.
Main effects of calcitonin:
- inhibition of the action of parathyroid hormone on bone tissue — suppression of bone resorption by osteoclasts;
- increase in calcium and phosphate excretion in the urine;
- overall — a decrease in the calcium level in the intercellular fluid.
Thus, calcitonin acts as a functional antagonist of parathyroid hormone.
Integral regulation of calcaemia
When blood calcium decreases, the parathyroid glands are activated → parathyroid hormone is released → bone resorption, renal Ca²⁺ reabsorption, and calcitriol synthesis are enhanced. Calcitriol additionally enhances the intestinal absorption of calcium and phosphates. When calcium increases, calcitonin is secreted, inhibiting bone resorption and enhancing renal calcium excretion. Prolonged imbalance of this system is a key link in the pathogenesis of osteoporosis, rickets, and secondary hyperparathyroidism in chronic renal failure.
Key points
- Calcium and phosphate levels are regulated by three hormones: parathyroid hormone, calcitriol, calcitonin.
- Parathyroid hormone is secreted by the parathyroid glands in response to a decrease in Ca²⁺.
- Parathyroid hormone activates osteoclasts via osteoblasts, increases Ca²⁺ reabsorption, and decreases phosphate reabsorption in the kidneys.
- Calcitriol is formed in three stages: skin → liver (25-hydroxylase) → kidneys (1α-hydroxylase).
- 1α-Hydroxylase is a key regulatory enzyme; it is activated by PTH and low Ca²⁺, and inhibited by calcitriol.
- Calcitonin is synthesized by C-cells of the thyroid gland during hypercalcemia.
- Calcitonin suppresses bone resorption and enhances renal calcium excretion.
- Disorders of this system underlie osteoporosis, rickets, and renal osteodystrophy.