INHIBITION OF THE ECDYSTEROID BIOSYNTHETIC-PATHWAY IN OVARIAN FOLLICLE CELLS OF LOCUSTA-MIGRATORIA

Inhibition of the terminal hydroxylation steps of ecdysteroid biosynth esis has been investigated in the ovarian follicle cells of the migrat ory locust, Locusta migratoria, using [H-3]2,22,25-tride-oxyecdysone a s substrate in an in vitro system. A series of cytochrome P450 inhibit ors have been examined and the effects of various structural character istics on their potency discussed. Several compounds known to have eff ects on ecdysteroids were investigated to determine whether they inhib ited the terminal stages of the biosynthetic pathway. The imidazole co mpounds KK42 and ICI-L-635 as well as buprofezin all inhibited biosynt hesis, with KK42 and ICI-L-635 preferentially inhibiting the C-22 hydr oxylase. This was also the case for the majority of the cytochrome P45 0 inhibitors, suggesting that the C-22 hydroxylase is the most sensiti ve of the terminal hydroxylases to inhibition. (C) 1994 Academic Press , Inc.