Monolayer cultures of human calcitonin-secreting cells (C-cells) have been derived from medullary thyroid carcinomas. The cultures were prepared from cell suspensions obtained by enzymatic digestion of surgical specimens of the tumor. Human calcitonin (hCT) secretion by these cells was studied using a specific radioimmunoassay for the hormone. The cultures could be used for reproducible secretion studies up to 40 days after their initiation; they demonstrated a linear rate of hormone secretion in the basal state for at least 4 h. Calcium, pentagastrin, and prostaglandin E2 (PGE2) each produced a marked increase (up to 7-fold) in hormone secretion. Magnesium had no apparent secretory effect; and compared to PGE2, PGF2alpha had only a small secretory effect. In addition to responding to specific secretagogues shown to regulate calcitonin secretion in vivo, the secretory effects of each of the secretagogues could be raipdly reversed. Therefore, these cultures of human C-cells exhibit secretory responses which are quantitatively and qualitatively similar to C-cells in vivo. Accordingly, such cultures provide a useful model to study the regulation of calcitonin secretion in human C-cells.

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