Regulation and Role of Nuclear Receptors during Larval Molting and Metamorphosis of Lepidoptera

SYNOPSIS. The regulation of the ecdysteroid-induced cascade of transcription factors by 20-hydroxyecdysone (20E) and juvenile hormone (JH) in the epidermis of the lepidopteran Manduca sexta is summarized. Both the levels and isoforms of the ecdysone receptor (EcR) and Ultraspiracle (USP) change during the molt. The 20E induction of MHR3, an orphan receptor that appears relatively late in the cascade, is dependent on the predominant intermolt isoforms, EcR-Bl and USP-1, and on the orphan receptor E75A which appears early in the cascade. The USP-2 isoform induced by 20E pairs with EcR-Bl but this heterodimer cannot up-regulate MHR3. Thus, the specific transcription factors induced by 20E are dependent on the particular isoforms present in the heterodimeric EcR/USP complex. Juvenile hormone modulates responses of the transcription factor cascade to 20E. For E75A, the presence of JH increased both its sensitivity to 20E and the accumulation of its mRNA, indicating that high E75A may be important for maintenance of the larval state. By contrast, JH prevented the 20E induction of the Broad Complex group of transcription factors which appear as the larval epidermis becomes pupally committed and are necessary for metamorphosis in Drosophila. During the decline of ecdysteroid, the orphan receptors, GRF and pFTZ-Fl, appear and may regulate transcription of dopa decarboxylase, a key enzyme in sclerotization of the new cuticle. Thus, the ecdysteroid-induced regulatory cascade is set in motion and regulated by the changing concentration and types of ecdysteroids and receptor isoforms. The presence of JH further modulates this cascade by acting selectively on the responses of specific factors and thus prevents the 20E-induced gene switching necessary for metamorphosis.