PMID- 15180384
OWN - NLM
STAT- MEDLINE
DCOM- 20040823
LR  - 20191210
IS  - 0730-7268 (Print)
IS  - 0730-7268 (Linking)
VI  - 23
IP  - 5
DP  - 2004 May
TI  - Effects of methoprene, its metabolites, and breakdown products on 
      retinoid-activated pathways in transfected cell lines.
PG  - 1305-10
AB  - Methoprene (isopropyl (2E,4E)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate) is 
      an insect juvenile hormone agonist that blocks metamorphosis in some insects. 
      Recent evidence suggests that a metabolite, methoprene acid, activates vertebrate 
      retinoid X receptors (RXRs), and may interfere with retinoic acid-regulated 
      developmental processes. Methoprene, methoxy-methoprene acid, and two major 
      breakdown products were tested for their ability to interfere with 
      retinoid-regulated pathways when using transfected cells. The CV-1 cells were 
      transiently transfected with genes encoding RXRs and response elements attached 
      to luciferase reporters, and retinoic acid-sensitive F9 cells were stably 
      transfected with retinoic acid receptor (RAR)/RXR response elements attached a 
      lacZ reporter (Sil-REM/beta-gal-NEO). Experiments confirmed that 
      methoxy-methoprene acid acted as a ligand for RXRs and was capable of activating 
      transcription through RAR/RXR response elements. However, neither methoprene nor 
      the breakdown products, 7-methoxycitronellal and 7-methoxycitronellic acid, 
      activated transcription in transfected CV-1 or F9 cells. Methoprene and 
      methoxy-methoprene acid may interfere with the conversion of all-trans-retinol 
      and all-trans-retinaldehyde to all-trans-retinoic acid in the F9-derived cell 
      line. Methoprene was as effective as the retinol dehydrogenase inhibitor citral 
      in blocking the retinol-induced transcription of RAR/RXR-regulated reporter 
      genes, whereas methoxy-methoprene acid blocked transcription stimulated by 
      retinaldehyde.
FAU - Schoff, Patrick K
AU  - Schoff PK
AD  - U.S. Environmental Protection Agency, Office of Research and Development, 
      National Health and Environmental Effects Research Laboratory, Mid-Continent 
      Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804, USA. 
      pschoff@nrri.umn.edu
FAU - Ankley, Gerald T
AU  - Ankley GT
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Environ Toxicol Chem
JT  - Environmental toxicology and chemistry
JID - 8308958
RN  - 0 (Acyclic Monoterpenes)
RN  - 0 (Juvenile Hormones)
RN  - 0 (Monoterpenes)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - 8B830OJ2UX (Methoprene)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - T7EU0O9VPP (citral)
SB  - IM
MH  - Acyclic Monoterpenes
MH  - Animals
MH  - Cell Line
MH  - Haplorhini
MH  - Juvenile Hormones/metabolism/*pharmacology
MH  - Luciferases/genetics/metabolism
MH  - Metamorphosis, Biological/drug effects
MH  - Methoprene/metabolism/*pharmacology
MH  - Mice
MH  - Monoterpenes/pharmacology
MH  - Receptors, Retinoic Acid/drug effects/metabolism
MH  - Retinoids/classification/*metabolism
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - beta-Galactosidase/drug effects/metabolism
EDAT- 2004/06/08 05:00
MHDA- 2004/08/24 05:00
CRDT- 2004/06/08 05:00
PHST- 2004/06/08 05:00 [pubmed]
PHST- 2004/08/24 05:00 [medline]
PHST- 2004/06/08 05:00 [entrez]
AID - 10.1897/03-117 [doi]
PST - ppublish
SO  - Environ Toxicol Chem. 2004 May;23(5):1305-10. doi: 10.1897/03-117.