1,25-Dihydroxyvitamin D3 silences 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 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 cAMP-dependent pathway which regulates peptide secretion.
Rogers
D G
DG
Department of Pediatrics, VA Medical Center, Houston, Texas 77030.
Cote
G J
GJ
Huang
E S
ES
Gagel
R F
RF
D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D013004:Somatostatin; D000242:Cyclic AMP; D002117:Calcitriol