A second plasma calcium-lowering peptide from the human calcitonin precursor


Calcitonin is a 3,500-molecular weight (MW) polypeptide whose main function in man is to protect the skeleton during growth, pregnancy and lactation1. It is secreted by C-cells which are localized in the thyroid in mammals, but may be present mainly in the ultimobranchial body and lung of more primitive vertebrates2. The hormone is also concentrated in the hypothalamus of several vertebrate species3,4, including man5, and in the primitive brain of the chordate Ciona intestinalis6,7. Based on cloning and subsequent analysis of recombinant DNA, recently we have reported the partial nucleotide sequence of the human calcitonin precursor mRNA8,9. This study showed that calcitonin resides towards the C-terminal end of its precursor protein, flanked by cryptic peptides of unknown significance. We now report that the synthetic C-terminal flanking peptide (PDN-21) predicted from the nucleotide sequence is highly active biologically—it approaches the potency of calcitonin in reducing the level of plasma calcium. As immunological evidence suggests that PDN-21 is synthesized in vivo and circulates in man, it may represent a novel hormonal cleavage product from the human calcitonin precursor with a physiological role in Ca2+ regulation.

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MacIntyre, I., Hillyard, C., Murphy, P. et al. A second plasma calcium-lowering peptide from the human calcitonin precursor. Nature 300, 460–462 (1982). https://doi.org/10.1038/300460a0

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