1, 25-dihydroxy vitamin D₃silences 3', 5'-cyclic adenosine monophosphate enhancement of somatostatin gene transcription in human thyroid C cells

Treatment of the somatostatin (SRIF)-producing TT cell line with 1, 25 dihydroxy vitamin D₃ (1, 25 D₃) lowered intracellular SRIF mRNA and peptide concentration. In separate experiments, the cAMP analog 8-(4-chlorophenylthio)-cAMP stimulated a rapid increase in SRIF mRNA content of the TT cells and SRIF peptide secretion. To determine whether 1, 25 D₃ could inhibit either the transcriptional or secretory effects of cAMP, TT cells were pretreated with 1, 25 D₃ for 4 days followed by treatment with the cAMP analog. Pretreatment with 1, 25 D₃ inhibited the cAMP-mediated increase of SRIF mRNA, but had no effect on the secretory response. We conclude that the ability of 1, 25 D₃ to silence SRIF gene expression is more potent than cAMP enhancer activity but that 1, 25 D₃ has no effect on that portion of the cAMP-dependent pathway which regulates peptide secretion.