Target of Cockroach Allatostatin in the Pathway of Juvenile Hormone Biosynthesis

Allatostatins, peptides with an YXFGL-amide C-terminus, cause a rapid and reversible inhibition of the sesquiterpenoid juvenile hormone III biosynthesis by cockroach corpora allata in vitro. Inhibition is relieved by farnesol and by mevalonate, and neither HMG-CoA reductase nor HMG-CoA synthesis (HMG-CoA synthase and acetoacetyl-CoA lyase) are inhibited by allatostatin. The neuropeptide is more effective as an inhibitor of JH III synthesis in glucose or amino acid-driven glands than in acetate-driven glands. Incorporation of label from acetate into JH III is increased whereas incorporation of label from glucose is decreased by allatostatin. Citrate is a very effective precursor for HMG-CoA synthesis in homogenates of corpora allata. We propose that inhibition of JH III biosynthesis by the tridecapeptide APSGAQRLYGFGL-amide occurs at the first committed step(s) of JH III synthesis, i.e. the transfer of 2C units from mitochondria to the cytoplasm by the tricarboxylate carrier and/or the ATP-citrate lyase.