Hormonal regulation and functional role of Drosophila E75A orphan nuclear receptor in the juvenile hormone signaling pathway

Ecdysone and juvenile hormone (JH) are important regulators of insect growth and development. While ecdysone initiates a transition from one developmental stage to another, JH determines the nature of the transition. How these two hormones interact at the molecular level is not known. Here we report the JH inducibility of the E75A nuclear receptor encoded by the E75 early ecdysone-inducible gene. In Drosophila S2 cells, E75A transcription is specifically activated by JH at concentrations well within the physiological range found in larvae and adults. The induction is rapid and does not require a concurrent protein synthesis, and thus represents a primary hormone response. Consistent with JH regulation, E75A mRNA levels are reduced in ovaries of apterous(4) mutant adults defective in JH secretion. Expression is rescued by topical methoprene application. We further provide evidence that ectopic E75A is sufficient to perform several functions in the JH signaling pathway. First, it can down-regulate its own transcription. Second, E75A can potentiate the JH inducibility of a secondary response gene, JhI-21. Finally, in the presence of JH, E75A can repress ecdysone activation of early genes including Broad-Complex. Based on these data, we propose a model for the role of E75A in the ecdysone-JH regulatory interplay. (C) 2004 Elsevier Inc. All rights reserved.