PMID- 8397452
OWN - NLM
STAT- MEDLINE
DCOM- 19931015
LR  - 20131121
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 122
IP  - 1
DP  - 1993 Sep
TI  - Induction of RAR-beta 2 gene expression in embryos and RAR-beta 2 transactivation 
      by the synthetic retinoid Ro 13-6307 correlates with its high teratogenic 
      potency.
PG  - 159-63
AB  - Vitamin A (retinol), its metabolite all-trans retinoic acid (RA), and many 
      synthetic analogs (retinoids) express variable potencies as teratogens. Although 
      biological activities of retinoids are mediated by nuclear RA receptors (RARs) 
      and retinoid X receptors (RXRs), it is not known if any of these receptors 
      mediate teratogenicity, and if the potency also depends on the nature of the 
      ligand-receptor interactions. Previous evidence has implicated that one specific 
      isoform, RAR-beta 2, does play a role in mediating retinoid teratogenicity. Here, 
      we employed an aromatic retinoid with a triene side chain, Ro 13-6307, to study 
      its interactions with RAR-beta 2 since its teratogenicity is much higher and its 
      accessibility to the embryo is much lower than RA. A fully teratogenic dose of Ro 
      13-6307 (10 mg-kg) given to pregnant mice preferentially elevated the level of 
      RAR-beta 2 mRNA in susceptible embryonic regions (maximal induction, 10- to 
      12-fold above control in limb buds) in a manner comparable to a fully teratogenic 
      dose of all-trans RA (100 mg-kg). Using the RAR-beta 2 promoter linked to a 
      reporter gene in cotransfection experiments, the efficacy of Ro 13-6307 and 
      RAR-beta 2 in transcription transactivation was found to be 30-40 times greater 
      than all-trans RA. Since the teratogenic potency of Ro 13-6307 is estimated from 
      a previous study to be 44-fold greater than all-trans RA, we suggest that the 
      teratogenicity of this synthetic retinoid is generally proportional to its 
      ability to enhance receptor function.
FAU - Soprano, D R
AU  - Soprano DR
AD  - Department of Biochemistry, Temple University School of Medicine, Philadelphia, 
      Pennsylvania 19140.
FAU - Tairis, N
AU  - Tairis N
FAU - Gyda, M 3rd
AU  - Gyda M 3rd
FAU - Harnish, D C
AU  - Harnish DC
FAU - Jiang, H
AU  - Jiang H
FAU - Soprano, K J
AU  - Soprano KJ
FAU - Kochhar, D M
AU  - Kochhar DM
LA  - eng
GR  - DK41089/DK/NIDDK NIH HHS/United States
GR  - HD20925/HD/NICHD NIH HHS/United States
GR  - HD27665/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Carrier Proteins)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
RN  - 79073-31-7 (Ro 13-6307)
SB  - IM
GS  - RAR-&Bgr;2
MH  - Animals
MH  - Carrier Proteins/*genetics
MH  - Embryo, Mammalian/*drug effects/metabolism
MH  - Fatty Acids, Unsaturated/toxicity
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - Mice
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Retinoic Acid
MH  - Stereoisomerism
MH  - Teratogens/*toxicity
MH  - Transcription, Genetic/drug effects
MH  - Transcriptional Activation/*drug effects
MH  - Tretinoin
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
AID - S0041-008X(83)71183-X [pii]
AID - 10.1006/taap.1993.1183 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1993 Sep;122(1):159-63. doi: 10.1006/taap.1993.1183.