Nongenomic and genomic actions of an insect steroid coordinately regulate programmed cell death of anterior silk glands of Bombyx mori

Abstract

The insect steroid hormone 20-hydroxyecdysone (20E) induces programmed cell death of larvaspecific
tissues at pupal metamorphosis. In the silkworm Bombyx mori, the anterior silk gland undergoes cell death in response to the metamorphic peak titer of ecdysteroids in vivo and also to 20E in vitro. Although 20E elicits early gene activation, an additional 20E stimulus is required for completion of cell death. This additional stimulus involves caspase-3-like protease activation, indicating that 20E also acts through a nongenomic mechanism. Studies using various inhibitors, agonists, and antagonists have shown that cell condensation is under the control of 20E genomic action, and that 20E nongenomic action begins with 20E binding to the putative membrane-bound ecdysone receptor, which is probably a G-protein-coupled receptor. This step is followed by a signaling pathway comprising phospholipase C/inositol 3,4,5-triphosphate/Ca2+/protein kinase C/caspase-3-like
protease, which induces DNA and nuclear fragmentation. Nuclear condensation is regulated by
signaling of calmodulin/calmodulin-dependent protein kinase II (CaMKII), but CaMKII activation is
independent of intracellular Ca2+ elevation. In addition, the genomic action of 20E is indispensable for
driving its nongenomic action, indicating that crosstalk between genomic and nongenomic action plays a significant role in 20E-induced cell death.