title: Induction of enzymes involved in molting hormone (ecdysteroid) inactivation by ecdysteroids and an agonist, 1,2-dibenzoyl-1-tert-butylhydrazine (RH-5849).
abstract: Molting in insects is regulated by molting hormones (ecdysteroids). The major active hormone, 20-hydroxyecdysone, is formed by ecdysone 20-monooxygenase-catalyzed hydroxylation of ecdysone. During times of decreasing hormone titers, inactivation occurs by several routes including (i) 26-hydroxylation and further oxidation to the 26-oic acid, (ii) formation of various conjugates (e.g. phosphates), and (iii) in Lepidoptera in particular, ecdysone oxidase-catalyzed formation of 3-dehydroecdysteroid, which is reduced to 3-epiecdysteroid, followed by phosphotransferase-catalyzed formation of phosphate conjugates. Administration of the nonsteroidal ecdysteroid agonist RH-5849 (1,2-dibenzoyl-1-tert-butylhydrazine), but not 20-hydroxyecdysone, to tobacco hornworm (Manduca sexta) resulted in induction of midgut cytosolic ecdysone oxidase and ecdysteroid phosphotransferase activities. In addition, both 20-hydroxyecdysone and RH-5849 caused induction of ecdysteroid 26-hydroxylase activity in midgut mitochondria and microsomes, whereas 20-hydroxylase was induced to a lesser extent by 20-hydroxyecdysone in mitochondria and by either RH-5849 or 20-hydroxyecdysone in microsomes. Commensurate with induction of the enzymes by ecdysteroid and RH-5849 is a requirement for RNA and protein synthesis, without precluding indirect mechanisms. These results indicate that molting hormone stimulates at least one universal route of its own inactivation by inducing ecdysteroid 26-hydroxylase activity and are discussed in relation to an analogous phenomenon observed for vitamin D inactivation in vertebrates.
authors.affiliation: Department of Biochemistry, University of Liverpool, Life Sciences Building, Crown Street, Liverpool L69 7ZB, United Kingdom.
authors.forename: D R
authors.initials: DR
authors.lastname: Williams
authors.forename: J H
authors.initials: JH
authors.lastname: Chen
authors.forename: M J
authors.initials: MJ
authors.lastname: Fisher
authors.forename: H H
authors.initials: HH
authors.lastname: Rees
mesh_terms: D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase; D002851:Chromatography, High Pressure Liquid; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003609:Dactinomycin / Q000494:pharmacology; D004440:Ecdysone / Q000378:metabolism*; D004441:Ecdysterone / Q000378:metabolism*; D004790:Enzyme Induction; D006834:Hydrazines / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D007536:Isomerism; D018402:Manduca; D009249:NADP / Q000378:metabolism; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019998:Racemases and Epimerases / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
chemical_list: D006834:Hydrazines; D007306:Insecticides; D011500:Protein Synthesis Inhibitors; C056565:1,2-dibenzoyl-tert-butylhydrazine; D003609:Dactinomycin; D004440:Ecdysone; D004441:Ecdysterone; D009249:NADP; D003513:Cycloheximide; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D019998:Racemases and Epimerases