INDUCTION OF ENZYMES INVOLVED IN MOLTING HORMONE (ECDYSTEROID) INACTIVATION BY ECDYSTEROIDS AND AN AGONIST, 1,2-DIBENZOYL-1-TERT-BUTYLHYDRAZINE (RH-5849)

Molting in insects is regulated by molting hormones (ecdysteroids). Th e major active hormone, 20-hydroxyecdysone, is formed by ecdysone 20-m onooxygenase-catalyzed hydroxylation of ecdysone. During times of decr easing hormone titers, inactivation occurs by several routes including (i) 26-hydroxylation and further oxidation to the 26-oic acid, (ii) f ormation of various conjugates (e.g. phosphates), and (iii) in Lepidop tera in particular, ecdysone oxidase-catalyzed formation of 3-dehydroe cdysteroid, which is reduced to 3-epiecdysteroid, followed by phosphot ransferase-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 (Man duca sexta) resulted in induction of midgut cytosolic ecdysone oxidase and ecdysteroid phosphotransferase activities, In addition, both 20-h ydroxyecdysone and RH-5849 caused induction of ecdysteroid 26-hydroxyl ase activity in midgut mitochondria and microsomes, whereas 20-hydroxy lase was induced to a lesser extent by 20-hydroxyecdysone in mitochond ria and by either RH-5849 or 20-hydroxyecdysone in microsomes, Commens urate with induction of the enzymes by ecdysteroid and RH-5849 is a re quirement for RNA and protein synthesis, without precluding indirect m echanisms, These results indicate that molting hormone stimulates at l east one universal route of its own inactivation by inducing ecdystero id 26-hydroxylase activity and are discussed in relation to an analogo us phenomenon observed for vitamin D inactivation in vertebrates.