Common phytochemicals are ecdysteroid agonists and antagonists: a possibleevolutionary link between vertebrate and invertebrate steroid hormones

Many plant compounds are able to modulate growth and reproduction of herbiv ores by directly interacting with steroid hormone systems. In insects, seve ral classes of phytochemicals, including the phytoestrogens, interfere with molting and reproduction. We investigated whether the anti-ecdysone activi ty may be due to interaction with the ecdysone receptor (EcR) using a repor ter-gene assay and a cell differentiation assay of an ecdysone-responsive c ell line, C1.8+. We tested rutin (delays molt in insects); four flavones: l uteolin and quercetin (metabolites of rutin), and apigenin and chrysin; and three non-flavones, coumestrol and genistein (both estrogenic) and tomatin e (alters molt in insects). None of the phytochemicals tested were ecdysone agonists in the reporter-gene assay, but the flavones were able to signifi cantly inhibit EcR-dependent gene transcription. In the C1.8+ cells, querce tin and coumestrol were mixed agonists/antagonists, while genistein, tomati ne and apigenin showed a synergistic effect with ecdysteroid in the reducti on of cell growth. We suggest that the rutin effects on molting in insects are most likely due to the metabolites, luteolin or quercetin, while tomati ne acts via a non-EcR pathway. Flavones not only interact with EcR and estr ogen receptor (ER), but also signal nitrogen-fixing bacteria to form root n odules. The NodD protein which regulates this symbiosis has two li.-and-bin ding domains similar to human ER alpha. The evolutionary significance of th ese findings are discussed. (C) 2001 Published by Elsevier Science Ltd.