Archives of Insect Biochemistry and Physiology 49:177–186 (2002) © 2002 Wiley-Liss, Inc. Effects of Hypocholesterolaemic Agents on the Expression and Activity of 3-Hydroxy-3- Methylglutaryl-CoA Reductase in the Fat Body of the German Cockroach Rafael Zapata, David Martín, Maria-Dolors Piulachs, and Xavier Bellés* In the fat body of adult Blattella germanica females, the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) during the first reproductive cycle is parallel to that of vitellogenin, suggesting a functional link between the mevalonate pathway, and vitellogenesis and reproduction. We have studied the effects of compactin and fluvastatin, two inhibitors of HMG-CoA reductase, on the expression and activity of the enzyme in the fat body, and on the ootheca formation, ootheca viability, and number of larvae per viable ootheca. Short-term assays showed that both compounds reduce the protein levels and enzymatic activity of HMG-CoA reductase, and long-term experiments revealed that fluvastatin impairs embryo development. Arch. Insect Biochem. Physiol. 49:177–186, 2002. © 2002 Wiley-Liss, Inc. KEYWORDS: Blattella germanica; cockroach; HMG-CoA reductase; fat body; vitellogenin; fluvastatin; compactin Department of Physiology and Molecular Biodiversity, Institut de Biologia Molecular de Barcelona (CID, CSIC), Barcelona, Spain Contract grant sponsor: DGICYT, Spain; Contract grant number: PB98-0472; Contract grant sponsor: CIRIT, Catalonia; Contract grant number: 1999 SGR 00186; Contract grant sponsor: Institut d’Estudis Catalans (IEC, Barcelona). *Correspondence to: Xavier Bellés, Department of Physiology and Molecular Biodiversity, Institut de Biologia Molecular de Barcelona (CID, CSIC), Jordi Girona 18, 08034 Barcelona, Spain. E-mail: xbragr@cid.csic.es Received 5 August 2001; Accepted 16 October 2001 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/arch.10018 INTRODUCTION In vertebrates, the main final product of the mevalonate pathway is cholesterol, and the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG- CoA reductase) plays a key role in its regulation (Goldstein and Brown, 1990). In contrast, insects do not synthesize cholesterol de novo (Beenakers et al., 1985) and the mevalonate pathway mainly leads to ubiquinone, dolichol, and juvenile hor- mone. Ubiquinone is involved in the electron transport chain, dolichol behaves as a donor of oligosaccharide residues in the glycosylation of pro- teins, and juvenile hormone regulates embryonic development, represses metamorphosis, and in- duces the synthesis of vitellogenin in most insect species (Nijhout, 1994). By analogy with vertebrate animals, HMG-CoA reductase has been postulated as a key enzyme in the regulation of the mevalon- ate pathway in insects (Feyereisen, 1985), and it has been studied at the molecular scale in the fruitfly Drosophila melanogaster (Gertler et al., 1988), the German cockroach Blattella germanica (Martínez- González et al., 1993), the moth Agrotis ipsilon (Duportets et al., 2000), and the bark beetle Ips paraconfusus (Tittiger et al., 1999). In B. germanica, Casals et al. (1996) reported the pattern of expression of HMG-CoA reductase in the fat body during the reproductive cycle of the adult female, in terms of mRNA, protein, and enzymatic activity. Protein levels and enzymatic activity peak in the middle of the cycle, which is