Parathyroid hormone and calcitonin: antagonist hormones
Maintaining blood $Ca^{2+}$ levels largely depends on the balance of two peptide hormones.
Parathyroid hormone (PTH) is secreted by the parathyroid glands and raises blood calcium levels through three pathways:
- In bone tissue: stimulates $Ca^{2+}$ mobilization, causing its release into the bloodstream.
- In the kidneys: enhances the reabsorption of calcium ions in the distal tubules.
- In the intestines: acts indirectly by activating the formation of calcitriol in the kidneys, which in turn stimulates $Ca^{2+}$ absorption.
PTH secretion is regulated by a negative feedback loop: as soon as blood calcium concentration rises, hormone production is suppressed.
Calcitonin is a polypeptide consisting of 32 amino acid residues with a single disulfide bond. It is synthesized by parafollicular cells (C-cells) of the thyroid gland and C-cells of the parathyroid gland. Unlike PTH, it lowers calcium levels by inhibiting its release from bones and stimulating urinary excretion. Calcitonin secretion increases during hypercalcemia and decreases when calcium is deficient.
Biosynthesis and mechanism of action of calcitriol
The active form of vitamin $D_3$ — calcitriol ($1,25(OH)_2D_3$) — is synthesized from cholesterol. A smaller portion of precursors comes from diet, but the main pathway begins in the skin.
Stages of conversion (Skin-Liver-Kidney scheme):
- Skin: 7-dehydrocholesterol undergoes non-enzymatic conversion to cholecalciferol under the influence of ultraviolet light. This breaks the B-ring of the steroid nucleus, forming a secosteroid structure (one hydroxyl group is added at the 3rd position).
- Liver: Under the action of 25-hydroxylase, cholecalciferol is hydroxylated at the 25th carbon atom, forming calcidiol (two -OH groups: 3, 25).
- Kidneys: The rate-limiting step takes place. The enzyme $1\alpha$-hydroxylase adds a third hydroxyl group, forming calcitriol (three -OH groups: 1, 3, 25).
Parathyroid hormone and low $Ca^{2+}$ levels activate the renal enzyme, while calcitriol itself inhibits it (feedback mechanism).
Calcitriol is transported through the blood bound to a carrier protein. Entering target cells (e.g., enterocytes), it binds to an intracellular receptor, interacts with chromatin, and alters the rate of translation. As a result, proteins that ensure calcium and phosphate absorption are synthesized.
Changes in plasma calcium concentration
The threshold of nerve and muscle cell excitability, the function of calcium pumps, and the activity of many enzymes depend on calcium levels.
- Hypocalcemia (a decrease in $Ca^{2+}$ levels) leads to increased neuromuscular excitability. Clinically, this manifests as hyperreflexia, convulsions, and laryngospasm.
- Hypercalcemia (an increase in $Ca^{2+}$ levels), conversely, causes a decrease in neuromuscular excitability. Severe nervous system disorders are possible: psychosis, stupor, and coma.
Parathyroid gland disorders
Hyperparathyroidism occurs due to excessive PTH secretion (e.g., caused by a tumor or glandular hyperplasia).
- Pathogenesis: excessive mobilization of calcium and phosphates from bone, increased calcium reabsorption, and enhanced renal excretion of phosphates.
- Laboratory findings: hypercalcemia, hypophosphatemia (in blood), and hyperphosphaturia (in urine).
- Symptoms: muscle weakness, decreased excitability, muscle pain, high risk of fractures (especially of the spine and hips), and kidney stone formation.
Hypoparathyroidism is parathyroid insufficiency. The main symptom is pronounced hypocalcemia. Patients suffer from tonic convulsion attacks (including spasms of the diaphragm and respiratory muscles), laryngospasm, and high neuromuscular conductivity.
Rickets: mineralization deficiency
Rickets is a childhood disease in which bone tissue is insufficiently mineralized due to calcium deficiency.
Causes:
- Dietary deficiency of vitamin $D_3$ or impaired absorption in the small intestine.
- Lack of sunlight (decreased synthesis in the skin).
- Genetic defects of the $1\alpha$-hydroxylase enzyme or calcitriol receptors.
Due to decreased intestinal calcium absorption, its blood concentration drops. This stimulates parathyroid hormone secretion (developing secondary hyperparathyroidism), which begins to draw calcium from the bones.
Clinical manifestations:
- Deformity of tubular bones and joints (bowing of the legs).
- Skull bone lesions.
- "Pigeon chest" (sternum protrudes forward).
- "Potbelly" (enlarged and protruding abdomen).
Briefly: answers to topical questions
What specific proteins does calcitriol stimulate in enterocytes to ensure calcium absorption?
Calcitriol stimulates the matrix biosynthesis of specific proteins based on mRNA in target cells (enterocytes). Crossing the plasma membrane and binding to the intracellular receptor, it acts on the genomic apparatus, initiating translation on cytoplasmic ribosomes. The main synthesized molecules include:
- Calbindin — a $Ca^{2+}$-binding protein that enhances calcium absorption in the intestine.
How does parathyroid hormone affect phosphate reabsorption in the renal tubules?
Parathyroid hormone inhibits phosphate reabsorption in the renal tubules (particularly the distal ones). This reduction in reabsorption leads to increased renal excretion of phosphates. As a result, phosphaturia develops in the body. In conditions with excessive secretion of this hormone (hyperparathyroidism), high concentrations of phosphates and calcium ions in the urine create favorable conditions for their crystallization and kidney stone formation.
Remember the sequence of active vitamin D synthesis using the abbreviation CLK: Skin (Koja) → Liver (Pechen) → Kidneys (Pochki). The initial steroid is converted into cholecalciferol, then into calcidiol, and finally into calcitriol.
Class and exam questions
Where is the rate-limiting step of calcitriol synthesis located?
In the kidneys. This is a hydroxylation reaction involving the enzyme 1α-hydroxylase, which is stimulated by parathyroid hormone and low calcium concentration.
What are the laboratory signs of primary hyperparathyroidism?
Blood tests show hypercalcemia and hypophosphatemia. Urinalysis determines hyperphosphaturia.
Why does secondary hyperparathyroidism develop in rickets?
Vitamin D deficiency reduces calcium absorption in the intestine. A drop in blood calcium levels triggers the compensatory production of parathyroid hormone, which begins to break down bone tissue to restore balance.
What else to study on this topic
- Mechanism of interaction between intracellular calcitriol receptors and chromatin
- Regulation of 1α-hydroxylase activity in the kidneys
- Synthesis of the high-molecular-weight calcitonin precursor protein
- Pathogenesis of kidney stone formation in hyperparathyroidism
- Clinical presentation of laryngospasm in hypocalcemia
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