Calcitonin and stanniocalcin: particular aspects of the endocrine regulation of calcium metabolism in fish and mammals.

The hypocalcemic and hypophosphatemic peptide calcitonin (CT) is secreted b y mammalian thyroid parafollicular cells and fish ultimobranchial body. Ove r a dozen species of CTs have been cloned and/or sequenced. They can be sep arated into three classes based on structural and biological similarities : teleost/avian, artiodactyl, and human/rat. In mammals, CT exerts its anti- hypercalcemic and hypophosphatemic effects by inhibiting osteoclastic bone resorption and venal tubular phosphate reabsorption, respectively. CT recep tors (CTRs) are members of a subfamily of seven-transmembrane domain, G pro tein-coupled receptors that include those for several other peptide hormone s. Basic amino acid substitutions within the CT molecule enhance potency, p robably by conferring a helical structure to the peptide. This might explai n the enhanced potency of fish CTs for mammalian CTRs. The presence and sec retion of salmon CT-like immunoreactive material have been described in bot h the murine and human central nervous systems, which possess CTRs. These f indings are consistent with a role for this peptide acting as a neurotransm itter in mammals. Stanniocalcin (STC) is another hypocalcemic hormone originally identified i n fish. In fish STC exerts its anti-hypercalcemic effect by regulating calc ium and phosphate transports by the gills, intestine and kidney. Although f ish ultimobranchial cells are much less responsive to the secretagogic effe cts of Ca2+ than mammalian parafollicular cells, the secretion of both CT a nd STC are positively regulated by extracellular calcium. STC has also been recently identified in humans and mts. It is released by some renal tubula r cells and might play a role in the regulation of phosphate metabolism. Ne vertheless, the true physiologic roles for CT in fish and STC in mammals, r espectively, remain unknown.