Medullary Thyroid Carcinomas Secrete a Noncalcitonin Peptide Corresponding to the Carboxyl-Terminal Region of Preprocalcitonin*

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Abstract
The amino acid sequence of human preprocalcitonin predicted from complementary DNA analyses indicates that the 32-amino-acid sequence of calcitonin is internally situated. Extending beyond the carboxyl-terminal proline of the calcitonin sequence is a 25-amino-acid segment which contains the tetrapeptide Gly-Lys-Lys-Arg linking calcitonin to the remaining 21 amino acids. Our objective was to examine whether human medullary thyroid carcinomas (MTCs) elaborate a noncalcitonin peptide corresponding to the carboxyl terminus of human preprocalcitonin. An acidic peptide identical to the predicted terminal 21-amino-acid sequence of human preprocalcitonin was synthesized for establishing a RIA. We used gel filtration, isoelectric focusing, and high pressure liquid chromatography to demonstrate immunoreactive peptide(s) with size, charge, and hydrophobicity similar to the 21-amino-acid synthetic peptide in MTCs and nonneoplastic thyroid. The immunoreactive noncalcitonin peptide was present in these tissue extracts in amounts approximately equimolar to calcitonin. A similar immunoreactive noncalcitonin peptide was detected in hypercalcitoninemic plasmas from MTC patients; such circulating immunoreactivity was undetectable (J Clin Endocrinol Metab56: 802, 1983)