RH 5849, a Nonsteroidal Ecdysone Agonist: Effects on a <i>Drosophila</i> Cell Line

TLDR

The steroid molting hormone 20‑hydroxyecdysone induces molting and metamorphosis in insects, and in ecdysone‑sensitive Drosophila Kc cells the insecticide RH 5849 mimics its action by forming processes, inhibiting proliferation, and inducing acetylcholinesterase. RH 5849 competes with [3H]ponasterone A for high‑affinity ecdysone receptor sites, and resistant Kc cell populations selected by growth in its presence become insensitive to both RH 5849 and 20‑hydroxyecdysone while showing reduced receptor titers, making it the first nonsteroidal ecdysone agonist despite lower potency.

Abstract

The steroid molting hormone 20-hydroxyecdysone is the physiological inducer of molting and metamorphosis in insects. In ecdysone-sensitive Drosophila Kc cells, the insecticide RH 5849 (1,2-dibenzoyl-1-tert-butylhydrazine) mimics the action of 20-hydroxyecdysone by causing the formation of processes, an inhibition of cell proliferation, and induction of acetylcholinesterase. RH 5849 also competes with [3H]ponasterone A for high-affinity ecdysone receptor sites from Kc cell extracts. Resistant cell populations selected by growth in the continued presence of either RH 5849 or 20-hydroxyecdysone are insensitive to both compounds and exhibit a decreased titer of measurable ecdysone receptors. Although it is less potent than 20-hydroxyecdysone in both whole-cell and cell-free receptor assays, RH 5849 is the first nonsteroidal ecdysone agonist.