Is calcitonin an important physiological substance?

That calcitonin (CT) at supraphysiological doses is hypocalcemic led to the mistaken conclusion that it was important for calcium homeostasis and this idea has persisted to this day. Despite these findings, there is no readily apparent pathology due to CT excess or deficiency and there is no evidence that circulating CT is of substantial benefit to any mammal. Mammalian CT at physiological doses is not essential and very likely the CT gene has survived because of the gene's alternate mRNA pathway to produce calcitonin-gene-related peptide found in neural tissues. CT is not involved in calcium homeostasis or any other important physiological function, except, possibly, as an adjunct to protection of the skeleton under conditions of calcium stress, and appears to be in the process of becoming vestigial. CT produced in other tissues has paracrine actions that modulate functions such as proton transport, acid-base balance, prolactin secretion, and gastrointestinal motility. C-cells in mammals evolved from the ultimobranchial body that secretes CT in all lower vertebrates. It is highly probable that changes in amino acid sequence during evolution are responsible for the loss of activity, as fish CT is about 40 times as potent as human CT. CT may have been very important to survival in seawater fish, but the presence of the parathyroid gland and other evolutionary changes occurring in tetrapods suggest that the function of CT is no longer important.