1. CALCITONIN
By: Gayle Seales

2. 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

3. 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

4. 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

5. Calcium Concentration Regulation
Calcium serum concentrations typically range 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

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

7. 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

8. 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.

9. 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

10. 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

11. 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

12. 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

13. 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