CALCITONIN By: Gayle Seales

What is Calcitonin? A 32 aimno acid peptide hormone Produced primarily by the Parafollicular cells or C Cells of the Thyroid Gland Acts to reduce Calcium serum concentration (and phosphate) in blood, and increase bone calcium absorption Acts in opposition to Parathyroid Hormone

Molecular Structure & Production of Calcitonin A polypeptide hormone, composed of a 32 amino acid chain, in a single alpha helix There is a disulfide bridge connecting the cysteines at position 1 and 7 to for a 7 amino-acid ring structure at the amino terminus The precursor of calcitonin, pre-procalcitonin (Pre-ProCT) contains 141 amino acids. Calcitonin originates from the calcitonin-I (CALC-I) gene on chromosome 11 The biosynthetic secretory pathway for calcitonin involves a complex series of modifications, and proteolytic processing that occurs in both the Golgi apparatus and later within secretory granules as the hormones is made & released from glandular cells

Additionally... The calcitonin gene transcript also encodes for Calcitonin Gene-Related Peptide (CGRP) CGRP does not bind to the Calcitonin receptor. CGRP is found in the thyroid, heart, lungs, GI Tract, and nervous tissue and acts as a neurotransmitter, not as a regulator of Calcium. CGRP is a potent vasodilator, and important to glomerular filtration rate

Calcium Concentration Regulation Calcium serum concentrations typically range 8.9 - 10.1 mg/dL, and can vary in genders and age. THREE MAJOR REGULATING HORMONES : Parathyroid Hormone - increases Calcium in plasma Calcitonin - decreases calcium in plasma Vitamin D - increases calcium and phosphate in plasma

Physiologic Importance of Calcium Calcium is a cation important for various functions: Nerve impulse Muscular contraction Blood coagulation Hormone secretion Intracellular adhesion Bone matrix

How does Calcitonin work? Via negative feedback mechanisms, Calcitonin regulates calcium blood concentrations in the: BONES - inhibits release of calcium from bone resorption KIDNEYS - inhibits calcium reabsorption in kidney tubules after glomerular filtration INTESTINAL - inhibits calcium absorption in the small intestine

Bone Resorption and Deposition Osteoblasts build bone matrix and lay down calcium deposits among osteocytes. Osteoclasts break apart bone matrix and release its minerals into blood circulation. Calcitonin does not influence osteoblasts, but does inhibit the activity of osteoclasts. This essentially retains calcium within bones and prevents loss of calcium into the blood, effectively lowering calcium concentration in the blood.

Kidney Absorption of Calcium Calcium absorption in the kidneys is regulated by calciotropic hormones Calcitonin and Parathyroid Hormone. Calcium is filtered at the glomerulus, with ua fraction of plasma calcium entering via the proximal tubule Calcitonin inhibits the reabsorption of Calcium from the tubules

Intestinal Absorption of Calcium Calcium in almost exclusively absorbed in the Small Intestine, via 2 pathways: Paracellular pathway (between cells) - passive transport and predominant absorption of Calcium when lumenal concentrations are high Transcellular (through the cell) - active transport, and highly influenced by the Calmodulin-Actin-Myosin-I complexes of the Microvilli Calcitonin inhibits the absorption of Calcium by intestinal cells

Calcitonin Receptor The Calcitonin receptor is a G Protein-Coupled Receptor that binds the hormone to its cell G-Proteins basically turn cells on or off, acting as molecular switches inside cells, transmitting signals from a stimuli outside the cell to it interior. This activates secondary messengers in the target cells

Medical Significance and Pharmacology Nodular thyroid disease, such as medullary thyroid cancer typically produce elevated calcitonin levels. These result in abnormalities of the parafollicular cells of the thyroid. Calcitonin can be administered as a SQ or IM injection, or nasal spray for: Osteoporosis - bone breakdown Hypercalcemia - too high blood calcium levels Paget’s Disease - excessive breakdown & irregular reformation of bone Bone Metastases - bone cancers

Overall... Calcitonin is…. A peptide hormone Regulates calcium concentration, bringing levels down Acts on the bones, kidneys, and intestines Can be used for as a treatment for various bone modeling problems