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

Margaret A. Harmon, Marcus F. Boehm, Richard A. Heyman, David J. Mangelsdorf

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

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 hinds 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.

Original languageEnglish (US)
Pages (from-to)6157-6160
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number13
DOIs
StatePublished - Jun 20 1995

Keywords

  • isoprenoids
  • juvenile hormone
  • pesticide
  • retinoic acid
  • retinoic acid receptor

ASJC Scopus subject areas

  • General

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