The influence of a P 450 inhibitor on methyl farnesoate levels in cockroach corpora allata, in vitro

Abstract

The levels of methyl farnesoate in isolated corpora allata from adult female Periplaneta americana have been determined over the gonotrophic activity cycle, by measuring the incorporation from radio-labelled methionine. There is a clear relationship between methyl farnesoate levels and the total rate of juvenile hormone biosynthesis in individual pairs of glands, although the data do not conform to a simple Michaelis-Menten curve. Methyl farnesoate levels rise 30-fold during the spontaneous activity cycle, but never reach a level causing saturation of the methyl farnesoate epoxidase (EC 1.14.14.-). A putative P 450 inhibitor [methyl 2E,6E-3,7-dimethyl-8-(3,4-methylenedioxyphenoxy)-octadienoate] not only inhibits juvenile hormone biosynthesis in vitro by spontaneously active glands ( EC 50 = 7 × 10 −6 M), presumably by direct inhibition of the epoxidase, but also inhibits the production of total methyl ester ( EC 50 = 1.2 × 10 −5 M). By contrast, there is no inhibition of total esterification when the glands are simultaneously provided with exogenous farnesoic acid, indicating that neither the P 450 inhibitor nor the ensuing high levels of methyl farnesoate cause inhibition of the farnesoic acid O- methyl transferase (EC 2.1.1.-). It is proposed that levels of methyl farnesoate in the corpus allatum are normally limited by a feed-back mechanism, which prevents saturation of the epoxidase, and that this operates on a step prior to the O- methyl transferase.