RH 5849, a nonsteroidal ecdysone agonist: effects on a Drosophila cell line.

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.