BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 15. INTEGRATION OF METABOLIC PATHWAYS. HORMONES

15.13. Parathyroid Hormone and Calcitonin

The primary regulators of Calcium and phosphorus METABOLISM in The Human Body are parathyroid hormone (parathormone, PTH), Calcitonin, and Vitamin D Group compounds (Fig. 15.18). The target Organs for these Hormones are Bone tissue, Kidneys, and the Small Intestine. In addition, other factors participate in the Regulation of Calcium and phosphorus Homeostasis, including cytokines, IGF-I, IGF-II, and platelet-derived growth factor.

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Fig. 15.18. Biological action of parathormone

PTH is synthesized in the Parathyroid glands as pre-proPTH, which contains 115 amino acid residues. During Processing, pre-proPTH is first converted into proPTH (90 amino acid residues) and subsequently into mature PTH, which consists of 84 Amino Acids (PTH_1-84). In the Liver, kidneys, bones, and the parathyroid glands themselves, PTH_1-84 is metabolized to yield C-terminal, N-terminal, and mid-region fragments. Both intact PTH and the N-terminal fragment exhibit hormonal activity. Specifically, this fragment is responsible for binding to receptors on target Cells. The rate of PTH secretion depends primarily on the serum Ca²⁺ concentration. G protein-coupled Ca²⁺ receptors are located On the surface of parathyroid cells. The principal function of PTH is to maintain constant Blood calcium levels. Even a slight drop in calcium concentration rapidly stimulates PTH secretion, which in turn promotes bone resorption, decreases renal calcium excretion, and enhances calcium Absorption in the small intestine.

PTH is a key regulator of bone remodeling. PTH receptors are present on osteoblasts (capable of proliferation; their main function is the synthesis of organic matrix Proteins) and osteocytes (mature, non-proliferating cells). Upon hormone binding, osteoblasts begin to secrete IGF-I and cytokines that activate osteoclasts, thereby enhancing bone resorption. An increase in serum calcium concentration is observed as early as 30–60 minutes after The stimulation of PTH secretion. Under conditions of persistently elevated PTH levels (hyperparathyroidism), bone resorption outpaces Bone Formation, leading to osteopenia (reduced bone mass). PTH also stimulates the Production of organic matrix components by osteoblasts; consequently, short-term administration of the hormone exerts an anabolic effect, with bone formation predominating.

PTH stimulates calcium reabsorption in the distal convoluted tubules of the kidneys, thereby reducing urinary calcium excretion. Furthermore, it stimulates the renal Synthesis of the active form of vitamin D, 1,25-dihydroxycholecalciferol, which is the primary driver of intestinal calcium absorption. Through the action of 1,25(OH)₂D₃, the concentration of extracellular Ca²⁺ is maintained at the level required for the mineralization of the bone organic matrix. A deficiency in 1,25(OH)₂D₃ impairs The formation of amorphous calcium phosphate and hydroxyapatite crystals, resulting in Rickets or Osteomalacia.

Calcitonin is a peptide consisting of 32 amino acid residues, synthesized by the parafollicular C-cells of The Thyroid Gland. Calcitonin secretion is upregulated by elevated blood calcium levels and is regulated by gastroenteropancreatic hormones, notably gastrin. Calcitonin acts as an antagonist to PTH. It inhibits bone resorption by suppressing osteoclast activity and stimulates osteoblasts, thereby favoring bone formation. Calcitonin also suppresses renal calcium reabsorption and inhibits its intestinal absorption. In women, the rate of calcitonin secretion depends on estrogen levels. Estrogen deficiency leads to decreased secretion, which accelerates bone resorption.