title: Forward and feedback regulation of cyclic steroid production in Drosophila melanogaster.
abstract: In most animals, steroid hormones are crucial regulators of physiology and developmental life transitions. Steroid synthesis depends on extrinsic parameters and autoregulatory processes to fine-tune the dynamics of hormone production. In Drosophila, transient increases of the steroid prohormone ecdysone, produced at each larval stage, are necessary to trigger moulting and metamorphosis. Binding of the active ecdysone (20-hydroxyecdysone) to its receptor (EcR) is followed by the sequential expression of the nuclear receptors E75, DHR3 and βFtz-f1, representing a model for steroid hormone signalling. Here, we have combined genetic and imaging approaches to investigate the precise role of this signalling cascade within theprothoracic gland (PG), where ecdysone synthesis takes place. We show that these receptors operate through an apparent unconventional hierarchy in the PG to control ecdysone biosynthesis. At metamorphosis onset, DHR3 emerges as the downstream component that represses steroidogenic enzymes and requires an early effect of EcR for this repression. To avoid premature repression of steroidogenesis, E75 counteracts DHR3 activity, whereas EcR and βFtz-f1 act early in development through a forward process to moderate DHR3 levels. Our findings suggest that within the steroidogenic tissue, a given 20-hydroxyecdysone peak induces autoregulatory processes to sharpen ecdysone production and to confer competence for ecdysteroid biosynthesis at the next developmental phase, providing novel insights into steroid hormone kinetics.
authors.affiliation: CGM, UPR 3404, CNRS, Gif sur Yvette 91190, France Université Pierre et Marie Curie, Paris 75005, France jparvy@snv.jussieu.fr montagne@cgm.cnrs-gif.fr.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Parvy
authors.affiliation: CGM, UPR 3404, CNRS, Gif sur Yvette 91190, France Université Paris-Sud 11, Orsay 91400, France.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: CGM, UPR 3404, CNRS, Gif sur Yvette 91190, France Université Paris-Sud 11, Orsay 91400, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Garrido
authors.affiliation: UPMC-UMR 1392, iEES Paris, Paris 75005, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Maria
authors.affiliation: UPMC-UMR 1392, iEES Paris, Paris 75005, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Blais
authors.affiliation: CGM, UPR 3404, CNRS, Gif sur Yvette 91190, France Université Paris-Sud 11, Orsay 91400, France.
authors.forename: Mickael
authors.initials: M
authors.lastname: Poidevin
authors.affiliation: CGM, UPR 3404, CNRS, Gif sur Yvette 91190, France Université Paris-Sud 11, Orsay 91400, France jparvy@snv.jussieu.fr montagne@cgm.cnrs-gif.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Montagne
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D008675:Metamorphosis, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000096:biosynthesis*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C106186:Hr3 protein, Drosophila; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013256:Steroids; D014157:Transcription Factors; C055469:ecdysone receptor; C080885:nuclear hormone receptor FTZ-F1 beta, Drosophila; C061375:Eip75B protein, Drosophila; D004440:Ecdysone
keywords: DHR3; Drosophila; Ecdysone; Nuclear receptor; Prothoracic gland