Interactions of methyl farnesoate and related compounds with a crustacean retinoid X receptor

Jun 3, 2009Molecular and cellular endocrinology

How methyl farnesoate and similar compounds interact with a crustacean hormone receptor

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Abstract

Methyl farnesoate does not activate the retinoid X receptor (RXR) in crustaceans but may enhance the response to ecdysteroids.

The crustacean RXR showed significant activation of gene expression in response to tributyltin.
Methyl farnesoate and other potential RXR ligands did not activate RXR on their own.
Co-transfection of RXR and EcR led to luciferase expression in response to ecdysteroids.
The presence of methyl farnesoate or similar compounds enhanced the activation of RXR:EcR by ecdysteroids.
This synergy was not dependent on the co-activator SRC-1 and did not correlate with male sex determination in daphnids.

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While a functional role for the sesquiterpenoid hormone methyl farnesoate in arthropods has been recognized for decades, the identification of a receptor that mediates the action of this hormone remains equivocal. Luciferase reporter assays were used in the present study to evaluate the ability of methyl farnesoate and other putative ligands to activate gene transcription associated with the retinoid X receptor (RXR) and RXR:EcR heterodimeric complexes from the crustacean (Daphnia magna). The daphnid RXR constructs, transfected into HepG2 cells along with the reporter construct, significantly activated luciferase gene expression in response to tributyltin indicating that the crustacean RXR is indeed ligand activated. However, RXR was not activated by methyl farnesoate or other putative RXR ligands. Cells co-transfected with the daphnid RXR and EcR produced luciferase in response to ecdysteroids and this activation was significantly enhanced when cells were also provided either methyl farnesoate or other putative RXR ligands. This synergy among RXR and EcR ligands was not dependent upon the co-activator SRC-1 and did not correlate to a physiological response of daphnids to juvenoid hormones (male sex determination). Results indicate that methyl farnesoate, along with compounds that are functionally similar to methyl farnesoate synergize with ecdysteroids to activate the RXR:EcR receptor complex. However, this effect appears to be unrelated to the ability of these compounds to stimulate male sex determination.

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Interactions of methyl farnesoate and related compounds with a crustacean retinoid X receptor

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