Calcitoninrelated

Calcitonin-related is a broad term used to describe topics connected with calcitonin, a peptide hormone produced by thyroid C cells, and with peptides and receptors derived from the calcitonin gene. The scope includes physiology, signaling pathways, receptor biology, and clinical applications, as well as related peptides such as calcitonin gene-derived peptides and the calcitonin gene-related peptide system, which has become central to migraine therapy.

Calcitonin biology and related peptides: Calcitonin lowers serum calcium primarily by inhibiting osteoclast-mediated bone resorption and by modestly increasing renal calcium excretion. The CALCA gene encodes calcitonin; through alternative splicing, it also produces α-CGRP in humans. The CALCB gene encodes β-CGRP. CGRP is a neuropeptide with strong vasodilatory effects and a significant role in migraine pathophysiology, whereas calcitonin acts mainly in calcium homeostasis and bone metabolism.

Receptors and signaling: The calcitonin receptor (CTR) is a G protein–coupled receptor that binds calcitonin. CTR can form receptor complexes with receptor activity-modifying proteins (RAMPs), influencing ligand specificity. The CGRP receptor is constructed from the calcitonin receptor-like receptor (CRLR) paired with RAMP1. Additional receptor assemblies, such as CRLR with RAMP2 or RAMP3, form adrenomedullin receptors, reflecting the broader network of calcitonin-related signaling.

Clinical relevance: Elevated calcitonin levels can serve as a tumor marker for medullary thyroid carcinoma and C-cell hyperplasia. Therapeutically, calcitonin has been used to treat hypercalcemia and osteoporosis, though its use has declined with newer agents. Conversely, CGRP and its receptor are targeted by monoclonal antibodies and small-molecule antagonists for migraine prevention, illustrating the clinical importance of calcitonin-related peptide signaling in modern medicine. Ongoing research continues to clarify the roles of calcitonin-related pathways in bone, vascular, and nervous system physiology.