PMID- 7981122
OWN - NLM
STAT- MEDLINE
DCOM- 19950103
LR  - 20190830
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 51
IP  - 3-4
DP  - 1994 Nov
TI  - The 1,25-dihydroxyvitamin D3 (VD) analogues MC903, EB1089 and KH1060 activate the 
      VD receptor: homodimers show higher ligand sensitivity than heterodimers with 
      retinoid X receptors.
PG  - 137-42
AB  - The nuclear receptor for 1,25-dihydroxyvitamin D3 (VD), VDR, belongs to the 
      nuclear receptor superfamily. This ligand-inducible transcription factor mediates 
      the genomic VD signalling pathways by binding to specific response elements in 
      the promoter region of VD regulated genes. Two types of natural VD response 
      elements are used as models for the VDR-mediated transcriptional activation: one 
      is bound by VDR-homodimers and is found in the human osteocalcin gene promoter, 
      and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as 
      in the mouse osteopontin promoter. Here, we demonstrate that the VD analogues 
      MC903, EB1089 and KH1060, previously shown to be potent regulators of 
      proliferation and differentiation, are able to act as ligands for VDR and replace 
      VD as a ligand in both nuclear signalling pathways. We found that they have 
      different potency and sensitivity in their ability to stimulate the 
      hormone-dependent promoter element. MC903 and EB1089 provide about 20% higher 
      induction of gene activity than VD in a gene reporter system, whereas KH1060 was 
      more sensitive, inducing transcription at about 100-fold lower doses than VD. 
      Interestingly, VD and its analogues induce VDR homodimer-mediated gene activity 
      at a 3- to 4-fold lower concentration than that of VDR-RXR heterodimers. This 
      suggests that the ligand concentration is an additional regulatory level in the 
      discrimination between signalling pathways involving homo- and heterodimeric 
      hormone receptors.
FAU - Carlberg, C
AU  - Carlberg C
AD  - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland.
FAU - Mathiasen, I S
AU  - Mathiasen IS
FAU - Saurat, J H
AU  - Saurat JH
FAU - Binderup, L
AU  - Binderup L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 131875-08-6 (KH 1060)
RN  - 143NQ3779B (calcipotriene)
RN  - 9007-49-2 (DNA)
RN  - FXC9231JVH (Calcitriol)
RN  - Q0OZ0D9223 (seocalcitol)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Calcitriol/*analogs & derivatives/pharmacology
MH  - DNA/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Ligands
MH  - Mice
MH  - Molecular Sequence Data
MH  - Receptors, Calcitriol/*drug effects/genetics/metabolism
MH  - Receptors, Retinoic Acid/*drug effects/genetics/metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/*drug effects/genetics/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured/drug effects/metabolism
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
AID - 10.1016/0960-0760(94)90086-8 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1994 Nov;51(3-4):137-42. doi: 
      10.1016/0960-0760(94)90086-8.