Ecdysteroids are steroid hormones, which coordinate major developmental transitions in insects. Both the rises and falls in circulating levels of active hormones are important for coordinating molting and metamorphosis, making both ecdysteroid biosynthesis and inactivation of physiological relevance. We demonstrate that Drosophila melanogaster Cyp18a1 encodes a cytochrome P450 enzyme (CYP) with 26-hydroxylase activity, a prominent step in ecdysteroid catabolism. A clear ortholog of Cyp18a1 exists in most insects and crustaceans. When Cyp18a1 is transfected in Drosophila S2 cells, extensive conversion of 20-hydroxyecdysone (20E) into 20-hydroxyecdysonoic acid is observed. This is a multi-step process, which involves the formation of 20,26-dihydroxyecdysone as an intermediate. In Drosophila larvae, Cyp18a1 is expressed in many target tissues of 20E. We examined the consequences of Cyp18a1 inactivation on Drosophila development. Null alleles generated by excision of a P element and RNAi knockdown of Cyp18a1 both result in pupal lethality, possibly as a consequence of impaired ecdysteroid degradation. Our data suggest that the inactivation of 20E is essential for proper development and that CYP18A1 is a key enzyme in this process.

Zooecdysteroids (arthropod steroid hormones) regulate the development of arthropods and probably many other invertebrates. Phytoecdysteroids are analogues occurring in a wide range of plant species, where they contribute to the deterrence of phytophagous invertebrates. The purpose of this short review is to summarise findings on the occurrence, metabolism and pharmacological effects of ecdysteroids in mammalian systems and to draw attention to their potential applications, particularly in gene-switch technology, where ecdysteroid analogues (steroidal and non-steroidal) can be used as effective and potent elicitors.

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Steroid molecules are present in all invertebrates, and some of them have established hormonal roles: this is the case for ecdysteroids in arthropods and, to a lesser extent, for vertebrate-type steroids in molluscs. Steroids are not only hormones, they may also fulfill many other functions in chemical communication, chemical defense or even digestive physiology. The increasing occurrence of endocrine disruption problems caused by environmental pollutants, which interfere in particular with reproductive physiology of vertebrates but also of invertebrates has made necessary to better understand the endocrine physiology of the latter and the role of steroids in these processes. So many attempts are being made to better understand the endocrine roles of steroids in arthropods and molluscs, and to establish whether they also fulfill similar functions in other invertebrate phyla. At the moment, both the precise identification of these steroids, the determination of their origin (endogenous versus exogenous) and of their mechanism of action are under active investigation. This research takes profit of the development of genome sequencing programs on many invertebrate species, which allow the identification of receptors and/or biosynthetic enzymes, when related to their vertebrate counterparts, but the story is not so simple, as will be exemplified by estrogen receptors of molluscs.