Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by parathyroid hormone and cAMP-agonists.
We studied the effect of parathyroid hormone (PTH) and activation of the cAMP signal pathway on vitamin D receptor (VDR) mRNA levels in the phenotypically osteoblast cell line UMR 106. PTH caused a time- and dose-dependent increase of the VDR mRNA content with a maximum after 2 h. After 24 h the VDR mRNA level in PTH-treated cells returned to control level. In contrast, the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced increase in VDR mRNA did not decline after 24 h. Inhibition of transcription with actinomycin D (10 micrograms/ml) completely abolished the PTH-induced increase of VDR mRNA and inhibition of translation with cycloheximide (1 microgram/ml) resulted in superinduction of VDR mRNA. The role of cAMP in the induction of VDR mRNA was studied with several agents acting via the cAMP pathway. Incubation for 2 and 4 h with forskolin, Bt2cAMP, PTHrP or prostaglandin E2 caused an increase in the level of VDR mRNA comparable to that caused by PTH. The calcium ionophore A23187 did not affect VDR mRNA level. The present study demonstrates that PTH and activation of the cAMP signal pathway cause up-regulation of VDR via induction of VDR gene expression. The effect of cAMP on the VDR gene is suggestive for a cAMP responsive element in the VDR gene.
van Leeuwen
J P
JP
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
Birkenhäger
J C
JC
Vink-van Wijngaarden
T
T
van den Bemd
G J
GJ
Pols
H A
HA
D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007700:Kinetics; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019379:Teriparatide; D014158:Transcription, Genetic / Q000187:drug effects*
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D019379:Teriparatide; D005576:Colforsin; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D002117:Calcitriol; D015232:Dinoprostone