Insect Moulting Hormone Ecdysteroids

An essential stage in the growth and development of insects is moulting or ecdysis. Growth is a discontinuous process, initiated at each stage by the moulting hormone (see Figure 1.5), a derivative of cholesterol. As there is not just a single compound involved in all insects, the group of hormones are called ecdysteroids. Although insects are unable to make squalene and do not possess the enzymes necessary for cyclization and sterol formation, they require cholesterol or an equivalent to make their moulting hormone. A protein prothoracotropic hormone (PTTH) stimulates the prothoracic gland to begin the synthesis that results in the formation of 20-hydroxyecydsone, the main hormone. The early stages of hydroxyecdysone synthesis are still not accurately known after some years of intensive study. Cholesterol is converted in the prothoracic gland to 7-dehydrocholesterol, probably through 7j3-hydroxycholesterol (Figure 7.14). The next step may be epoxidation to 7-dehydrocholesterol 5,6a-epoxide. By three more steps not yet clear, the epoxide is re-arranged to a 6-ketone, an a-hydroxyl group is introduced at C-14, and the 3p-OH is oxidized to a ketone. The first well established intermediate is 3p,14a-dihydroxycholest-7-en-6-one (A in Figure 7.14). From here it seems that two sequences run in parallel, the relative amounts of each varying with species. In one series, the 3f3-hydroxyl is oxidized to a ketone and we have a 3-deoxy-group. The other retains the 3[3-hydroxyl, but the two routes seem to be interconnected. Certainly the next step for each sequence is hydroxylation at C-20, followed by C-2. All of this occurs in the prothoracic gland. The end product in the gland is ecdysone, the first compound that was isolated, and thought for a time to be the hormone. Later it was found that hydroxylation of ecdysone at 20(S), which occurs in the peripheral tissues, was necessary to give 20-hydroxyecdysone, the true hormone. The hydroxyl groups are inserted by cytochrome P450 enzymes. The enzyme for the last step, in the peripheral tissues, ecdysone 20-mono-oxygenase (and NADPH) has been studied in great detail.

The story of the moulting hormone is not so neat and clear-cut as that of the juvenile hormone. There are a number of compounds of similar structure, all called ecdysteroids. There are plant-eating insects in at least four orders (Diptera, Coleoptera, Hemiptera and Hymenoptera) including the honeybee Apis mellifera, that are unable to remove the side-chain alkyl groups of plant sterols, and use makisterone A as their moulting hormone (Figure 7.15). It has the structure of 20-hydroxyecdysone, but with an extra 24(JR)-methyl group. Ecdysteroids are also found in mature ovaries and pass into eggs, and stored there as conjugates, that is, either phosphate esters or esters of fatty acids, attached through the C-22

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