Thyroid C-cells have the capacity to produce a variety of peptides, as do C-cell tumors. The cellular content of one such peptide, somatostatin, is restricted to a minority of C-cells in rat and human. We set out to clarify whether the synthesis of somatostatin is equally restricted and to study changes that occur in somatostatin synthesis with age. We used immunocytochemistry to localize somatostatin and calcitonin in conjunction with in situ hybridization, using digoxigeninlabeled oligoprobes to localize somatostatin and calcitonon calcitonin, and somatostatin synthesis, as shown by mRNA content, is limited to the subset of cells containing immunoreactive somatostatin. The numbem of C-cells in general and of the subset synthesizing somatostatin increase between juvenile and adult animals, but the somatostatin cells remain confined to a small area of the gland. These findings support the proposal that somatostatin production is not facultative, but that C-cells differentiate into two distinct sub-
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