Differential regulation of the coexpressed calcitonin/alpha-CGRP and beta-CGRP neuroendocrine genes.

The rat calcitonin/alpha-CGRP and beta-CGRP genes are members of a neuroendocrine gene family that are coexpressed in a distinct cell-specific pattern. The alpha- and beta-CGRP gene sequences predict highly related peptides that differ by only a single amino acid. Using rat medullary thyroid carcinoma cells as an in vitro system for testing hormone responsiveness, we have shown that the calcitonin/alpha-CGRP and beta-CGRP genes are differentially regulated. The synthetic glucocorticoid, dexamethasone, caused a 2- to 5-fold increase in calcitonin and alpha-CGRP mRNAs due to an increase in the nuclear transcription rate. In contrast, the levels of beta-CGRP mRNA did not significantly change following dexamethasone treatment. Differential regulation within neuroendocrine gene families might be a common mechanism for generating functionally similar peptides in response to a variety of hormonal signals.