Activation of mammalian retinoid X receptors by the insect growth regulator methoprene

We report that methoprene and its derivatives can stimulate gene transcription in vertebrates by acting through the retinoic acid-responsive transcription factors, the retinoid X receptors (RXRs). Methoprene is an insect growth regulator in domestic and agricultural use as a pesticide. At least one...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (13), p.6157-6160
Main Authors: Harmon, M A, Boehm, M F, Heyman, R A, Mangelsdorf, D J
Format: Article
Language:English
Subjects:
Animals
beta-Galactosidase - biosynthesis
Binding, Competitive
Biochemistry
Cell Line
Cercopithecus aethiops
DNA-Binding Proteins
Drosophila
Drosophila melanogaster
Fungal Proteins - biosynthesis
Fungal Proteins - metabolism
Gene Expression - drug effects
Genes
Insects
Kidney
Kinetics
Luciferases - biosynthesis
Luciferases - metabolism
Methoprene - pharmacology
Receptors, Retinoic Acid - biosynthesis
Receptors, Retinoic Acid - drug effects
Receptors, Retinoic Acid - metabolism
Recombinant Proteins - biosynthesis
Recombinant Proteins - drug effects
Recombinant Proteins - metabolism
Retinoid X Receptors
Retinoids - metabolism
Saccharomyces cerevisiae Proteins
Transcription Factors - biosynthesis
Transcription Factors - drug effects
Transcription Factors - metabolism
Transcription, Genetic - drug effects
Transfection
Vertebrates
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Summary:We report that methoprene and its derivatives can stimulate gene transcription in vertebrates by acting through the retinoic acid-responsive transcription factors, the retinoid X receptors (RXRs). Methoprene is an insect growth regulator in domestic and agricultural use as a pesticide. At least one metabolite of methoprene, methoprene acid, directly binds to RXR and is a transcriptional activator in both insect and mammalian cells. Unlike the endogenous RXR ligand, 9-cis-retinoic acid, this activity is RXR-specific; the methoprene derivatives do not activate the retinoic acid receptor pathway. Methoprene is a juvenile hormone analog that acts to retain juvenile characteristics during insect growth, preventing metamorphosis into an adult, and it has been shown to have ovicidal properties in some insects. Thus, a pesticide that mimics the action of juvenile hormone in insects can also activate a mammalian retinoid-responsive pathway. This finding provides a basis through which the potential bioactivity of substances exposed to the environment may be reexamined and points the way for discovery of new receptor ligands in both insects and vertebrates.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.13.6157