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1,25-Dihydroxyvitamin D₃ Silences 3',5'-Cyclic Adenosine Monophosphate Enhancement of Somatostatin Gene Transcription in Human Thyroid C Cells

Laboratory of Molecular and Cellular Endocrinology, Departments of Pediatrics, Medicine and Cell Biology, VA Medical Center and Baylor College of Medicine Houston, Texas 77030

Address requests for reprints to: Dr. Robert F. Gagel, Laboratory of Molecular and Cellular Endocrinology, VA Medical Center (111E), 2002 Holcombe Boulevard, Houston, Texas 77030.

Abstract

Treatment of the somatostatin (SRIF)-producing TT cell line with 1,25 dihydroxyvitamin 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 cAMPdependent pathway which regulates peptide secretion.

FOOTNOTES

This work was supported by Career Development and Merit Review grants from the Veterans Administration.

Received for publication October 20, 1988. Revision received December 20, 1988. Accepted for publication December 21, 1988.

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