title: Comprehensive physiology and toxicology of ecdysogens--The metabolically activated porphyrin-ecdysteroid complexes in insects.
abstract: The polyhydroxylated derivatives of 6-keto,7-dehydrocholesterol (ecdysone, ecdysteroids, Ecd) are natural compounds widely distributed in plants. They exhibit strong anabolic, vitamin D-like, pharmacological effects in vertebrate animals and in the human body. In the larval stages of insects, injections of pure Ecd cause serious pathophysiological, "hyperecdysonic" syndromes associated with neuromuscular paralysis, premature cuticular apolysis and complete inhibition of ecdysis. Ecds do not penetrate insect cuticle. For this reason, all previous attempts to induce ecdysone responses by topical applications of Ecd failed. In this work, we tried to induce the topical effects of Ecd by preparation of more lipophilic complexes, with 2 or 4 molecules of 20-hydroxyecdysone (E20) attached to a relatively large nucleus of the porphyrin. The resulting porphyrin-E20 complexes (ecdysogens) have been subjected to standardised assays for ecdysone activity in the ligatured larvae ("dauerlarvae") of the greater waxmoth (Galleria mellonella). Similarly like the free E20 alone, porphyrin-E20 complexes had no effect when applied on the body surface or administered in the larval diet. When injected, however, they exhibited delayed effects, but the adverse ("hyperecdysonic") pathophysiological syndromes were reduced or abolished. It is concluded, therefore, that the replacement of pathophysiological, precocious or "hyperecdysonic" moults by the larval-pupal transformation, was due to successive metabolic liberation of the biologically active, free E20 from the porphyrin-E20 complex. The biological status of Ecd does not agree with their definition as the prothoracic gland (PG) hormone of insects, nor with the assumptions about a growth hormone of plants. A possibility that the most important status of Ecd may depend on the pharmacological properties of a sterolic D6 vitamin has been discussed.
authors.affiliation: Institute of Entomology, Czech Academy of Sciences, Drnovská 507, 16100, Praha 6, Czech Republic. Electronic address: slama@entu.cas.cz.
authors.forename: Karel
authors.initials: K
authors.lastname: Sláma
authors.affiliation: Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus.
authors.forename: Halina
authors.initials: H
authors.lastname: Zhylitskaya
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004441:Ecdysterone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D007814:Larva / Q000187:drug effects; D007915:Lepidoptera / Q000187:drug effects / Q000502:physiology*; D008675:Metamorphosis, Biological / Q000187:drug effects; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D011679:Pupa / Q000187:drug effects
chemical_list: D011166:Porphyrins; D004441:Ecdysterone
keywords: 20-hydroxyecdysone (E20); Ecdysone; Ecdysone bioassays; Ecdysteroids (Ecds); Galleria mellonella; Hyperecdysonic syndromes; Neuromuscular paralysis by Ecd