cAMP signaling can antagonize potent glucocorticoid post-transcriptional inhibition of stanniocalcin gene expression.

Stanniocalcin (STC) is a glycoprotein hormone first discovered in fish as a homeostatic regulator of calcium and phosphate transport; it has recently been discovered in mammals, in which it appears to have a similar role. It has also been implicated in a number of different physiological processes through correlative studies, but the factors regulating its production have not been elucidated. In this report, we show that steady-state STC mRNA levels in the mouse corticotrope tumor line, AtT-20, were exquisitely sensitive to glucocorticoids. Hydrocortisone and dexamethasone (Dex) induced a dramatic reduction in steady-state STC mRNA levels in AtT-20 cells through a post-transcriptional mechanism. Similarly, glucocorticoids down-regulated STC mRNA levels in the human fibrosarcoma cell line, HT1080. The specificity of the glucocorticoid-mediated decrease in STC mRNA abundance was shown using the glucocorticoid receptor antagonist, RU-486. Activation of the cAMP-signaling pathway in glucocorticoid-cultured AtT-20 cells transiently restored STC gene expression. Treatment of AtT-20 cells with the transcriptional inhibitor, actinomycin D, rescued steady-state STC mRNA levels from Dex-induced repression, indicating that the Dex-mediated decrease in STC gene expression requires current gene transcription. Taken together, these results describe a unique model system in which cAMP-stimulated events can reverse post-transcriptional repression of gene expression by glucocorticoids.