The growth and development of insects is regulated through the secretion of internal ductless glands, i.e., hormones. Basically, three types of hormones are involved in insect development. The brain hormone or prothoracicotropic hormone, secreted by the neurosecretory cells of the brain, activates the prothoracic glands to secrete another hormone called moulting hormone (MH) or ecdysone.
Moulting hormone is necessary for each of the immature moults which must take place for insects to grow. The third hormone, juvenile hormone (JH), is secreted by the gland corpora allata and regulates the juvenile characters in insects. In the presence of high titer of JH, a larva moults into a larva, while at a low titer of JH, it moults into a pupa. In the absence of JH, pupa moults to become adult.
Two other hormones which also play a role in development are the eclosion and tanning hormones. The eclosion hormone, released by the brain, controls the process of eclosion in insects, while the tanning hormone or bursicon produced by neurosecretory cells of the brain or abdominal ganglia regulates the process of tanning and sclerotization of the new cuticle.
Exploitation of hormonal regulation for growth of insects in pest management are described below:
Exploitation of Brain Hormones:
Chemical messengers produced by the central nervous system to regulate various events in the body are known as brain hormones or neurohormones. The first neuropeptide, proctolin, was isolated from Periplaneta Americana (Linnaeus) in 1975 and since then 50 such structures have been isolated from different insects.
There are several promising approaches in which the information on insect neuropeptides may be utilized to the detriment of insects, viz.-
(i) The design of peptide mimics that can penetrate the insect cuticle or gut and block or overstimulate the peptide-mediated response at the target cell,
(ii) Development of control agents that interfere with the secretion of a neuropeptide, and
(iii) Incorporation of neuropeptide producing genes into microorganisms will make large scale production economical and also help in overcoming stability and penetration problems.
Exploitation of Juvenile Hormones:
The role of juvenile hormone (JH) in the growth of insects was recognized at least 60 years ago when Prof. C.M. Williams reported the possibility of its use in upsetting insect development. Till now, six closely related naturally occurring JHs have been isolated from insects. However, the natural JHs per se have limited scope in pest management because these are unstable to UV light and are rapidly metabolized by insects.
Therefore, the juvenile hormone analogue (JHA) synthesis was directed towards the stabilization of the molecules. Some of the earlier compounds showing promise as pest control agents were methoprene and hydroprene, and later on fenoxycarb and pyriproxyfen were commercialized.
The JHAs have been tested in large scale trials for the control of various pests of agriculture, forestry and public health importance. Five different formulations of methoprene are available for the control of mosquitoes, manure breeding flies, cigarette beetle, pharaoh’s ant, fungus gnat and fleas. Another JHA, fenoxycarb is registered in Switzerland for the control of several fruit pests.
Foliar application of fenoxycarb on cotton has provided satisfactory control of Helicoverpa zea (Boddie) and Heliothis virescens (Fabricius) in USA. Pyriproxyfen has proved effective against a number of sucking pests including whitefly, Dialeurodes citri (Ashmead); Thrips palmi Karny, California red scale, Aonidiella aurantii (Maskell) and cottony cushion scale, Iceiya purchasi Maskell.
A newer analogue, diofenolen, has been found highly effective for the control of scale insects and lepidopterous pests attacking a number of fruit crops. NC-196, a derivative of benzyl pyridazinone has shown good systemic and contact activity against brown planthopper of rice.
The exogenous applcation of JHAs is effective only when the endogenous JH titer in insects is low. This leaves the larval/nymphal stages of most of the insects unaffected. This limitation could be overcome by blocking the biosynthesis of natural JHs. The chemicals exhibiting this property are called antijuvenile hormone agents (AJHAs) or JH antagonists.
Interestingly, AJHAs were also initially isolated from a plant, Ageratum houstonianum Mill. These compounds designated as precocene I and II induced precocious metamorphosis in the milkweed bug, Oncopeltus fasciatus (Dallas). Another related compound precocene III was isolated from Ageratum conyzoides L.
Apart from precocenes, several other compounds like ETB and EMD act as JH antagonists. More recently, many synthetic furanyl compounds have been reported to possess AJH activity against O. fasciatus. The exogenous application of AJHAs to insects not only shortens the life cycle of immature stages but also results in diminished feeding.
Further, precocious males are unable to mate and inseminate normal females, while precocious females are sterile. AJHAs are thus effective against different developmental stages of insects which generally exist simultaneously in the field.
Chitin Synthesis Inhibitors:
A new class of insecticides was developed accidently when the insecticidal activity of benzoylphenyl urea (BPU) analogues was discovered around 1970 by the Philips-Duphar Company. One of the first analogues was code-named DU 19.111 which resulted from the combination of the herbicide dichlobenil with the urea herbicide diuron and possessed interesting insecticidal properties against several insect species.
Structural optimization resulted in the production of diflubenzuron [1-(4-chlorophenyl)-3-2-(2, 6-difluorobenzoyl) urea] which was commercialized under the name of Dimilin. Later, other bioactive molecules like BAY SIR 8514 and IKI 7899 (chlorfluazuron) were successfully commercialised.
Chitin synthesis inhibitors interfere with production of chitin, the structural polysaccharide found in insect cuticle, and thus affect the integrity of insect exoskeleton. Exposure causes improper attachment of the new cuticle during moulting and produces a cuticle that lacks some of the layers that normally occur.
Most larvae die from ruptures of the new malformed cuticle, desiccation, starvation or predation. Scientists investigating the new derivatives of herbicide, diclobenil, discovered CSIs accidentally. It was found that 1 – (2, 6-dichlorobenzoyl)-3-(3, 4-dichlorophenyl) urea (DU 19.111) possessed interesting insecticidal properties against several species of insects.
Thereafter, a large number of structural analogues were prepared and screened against a variety of insect pests. Diflubenzuron [1-(4-chlorophenyl)-3-(2, 6-difluorobenzoyl) urea] was the most successful analogue of the series and is effective against insect pests belonging to Coleoptera, Diptera and Lepidoptera.
Subsequently, more potent benzoylphenylureas (BPUs) like BAY SIR 8514, chlorfluazuron, lufenuron have been developed and they are very effective in controlling insect pests of cotton, maize and vegetable crops such as Spodoptera and Helicoverpa spp.
A new BPU insecticide, novaluron, has somewhat more contact and translaminar activity as compared with other BPUs, and cyromazine thereby affecting whiteflies and leafminers, in addition to lepidopteran and coleopteran larvae.
The benzoyl phenyl urea (BPU) analogues are compounds with selective properties, affecting the larval stage. They mainly act as stomach toxicants and kill insects at the time of moulting. However, in some species they suppress fecundity and exihibit ovicidal and contact toxicity.
The BPU analogues block the terminal polymerization step catalyzed by the enzyme chitin synthase during the process of biosynthesis of chitin. However, the exact site of action is not yet clearly understood and a number of interesting hypotheses have been put forward to explain the effects produced by the application of BPU analogues.
The most plausible explanation so far is that BPU analogues block the availability of substrates at the active sites of the membrane bound enzyme, chitin synthase, probably by altering membrane permeability. These compounds also inhibit a number of other enzymes and DNA biosynthesis in larval epidermal cells.
BPUs generally affect the larval stages of insects, which synthesize chitin during their moulting processes. Hence, the adults of beneficial species, predators and parasitoids, are seldom affected. For this reason, BPUs are considered important components in IPM programmes.
Another compound, buprofezin, is a thiadizine like compound with long residual activity that also acts as chitin synthesis inhibitor. It has both contact and vapour activity, and acts on nymphal stages of sucking insects such as leafhoppers, planthoppers and whiteflies. Its mode of action resembles that of BPUs, although its structure is not analogous.
The compound inhibits incorporation of 3H-glucose and N-acetyl-D-3H-glucosamone into chitin. Because of chitin deficiency, the procuticle of the whitefly nymph loses its elasticity and the insect is unable to molt. As in case of BPUs, buprofezin is effective against immature stages and not adults. The compound has a mild effect on natural enemies and is an important component of IPM programmes for managing whiteflies in cotton, vegetables and ornamental plants.
In addition to BPU analogues, several other groups of compounds have also been reported to act as CSIs. Plumbagin is a naturally occurring CSI present in the roots of a tropical medicinal shrub, Plumbago capensis Thunb. It has been reported to possess novel mode of action like chitin and ecdysteriod inhibition thereby leading to growth inhibition in insects.
Recent investigations have revealed that plumbagin possesses high ovicidal activity against eggs of Dysdercus koenigii (Fabricius), Spodoptera litura (Fabricius), Corcyra cephalonica (Stainton) and Plutella xylostella (Linnaeus). Besides its activity as a CSI, plumbagin is toxic to S. litura, P. xylostella and Helicoverpa armigera (Hubner) larvae, and adults of Myzus persicae (Sulzer). Toxicity of plumbagin was at least 3-fold higher for winged than apterous adults in case of topical assays, and at least 1645-fold higher for pterous than that for apterous aphids in residual film assays.
Chitin synthesis inhibitors belonging to the acyl urea group have been used commercially for the control of a number of foliage feeders and tissue borers. Satisfactory control of cabbage looper, Trichopulsia ni (Hubner); cotton leaf perforator, Bucculatrix thurberiella Busck and Egyptian cotton leafworm, Spodoptera littoralis (Boisduval), damaging cotton crop has been obtained with diflubenzuron.
Foliar application of diflubenzuron has shown excellent residual activity against eggs of Helicoverpa armigera (Hubner) and Spodoptera litura (Fabricius). Some new chitin synthesis inhibitors like XRD- 473, IKI-7899 and IGR-1055 have shown excellent larvicidal activity against H. armigera. Teflubenzuron has been found to posse’s high ovicidal action against Cydia pomonella (Linnaeus) on apple.
Buprofezin has been found promising against several sucking pests. Plumbagin is a naturally occurring chitin synthesis inhibitor present in the roots of a tropical medicinal shrub, Plumbago capensis Thunberg and it inhibits ecdysis in several lepidopteran pests including Pectinophora gossypiella (Saunders), Helicoverpa zea (Boddie) and Heliothis virescens (Fabricius).
Exploitation of Moulting Hormones:
Moulting hormones (MHs), represented by ecdysone, ecdysterone and other ecdysteroids are steroidal compounds secreted by prothoracic glands and are responsible for normal moulting, growth and maturation of insects. The exogenous application of phytoecdysteroids leads to an increased titre of ecdysone in insects, which cannot be metabolized or excreted rapidly enough to prevent hormonal imbalance resulting in moulting promotion and death of insects.
For instance, phytoecdysteriods isolated from the seeds of Diploclisia glaucescens (Bl.) Diels showed MH activity against the larvae of European corn borer, Ostrinia nubilalis (Hubner). Similarly, the ecdysterone isolated from the mature stem of D. glaucescens showed insecticidal activity against the groundnut aphid, Aphis craccivora Koch.
The extracts from dried parts of Ajuga reptans L. and A. remota strongly influence the metamorphosis of Epilachna varivestis Mulsant mimicking the growth regulatory effects of ecdysteroids. Likewise, a methanol extract of the plant, Vitex madiensis Oliver, characterised as 20-hydroxyecdy-sone, when incorporated in the diet of larvae of Spodoptera frugiperda (J.E. Smith) and Pectinophora gossypiella (Saunders) prevented normal moulting and caused death.
In recent years, several nonsteroidal bisacylhydrazine ecdysone agonists have been synthesized. The first ecdys- teroid agonist was discovered in 1983 and subsequent chemical modification of this early lead produced a simple and slightly more potent analogue, RH-5849, followed by other more potent and cost-effective analogues like tebufenozide, halofenozide, methoxyfenozide and chromafenozide.
These chemicals are much more potent than 20-hydroxyecdysone in inducing molting. They are also known to reduce feeding and weight gain. In lepidopteran insects, a lethal moult is induced following administration of the ecdysone agonist and the insect dies trapped within the exuvial cuticle.
Feeding stops 4-6 hours after ingestion of toxic doses of the agonist, and molting is initiated in the absence of an ecdysteroid increase. Usually, the insect dies in the slipped head capsule stage following onset of apolysis. However, supernumerary larval molts may also occur, when the JH titer is high.
Ecysteroid agonists have been demonstrated to be active against many lepidopterans including Manduca sexta (Johannsen), Pieris brassicae (Linnaeus), Plodia interpunctella (Hubner), Spodoptera exempta (Walker), S. littoralis (Boisduval) and S. litura (Fabricius). RH-5992 (tebufenozide) is more toxic to lepidopteran larvae than RH-5849.
RH-0345 (halofenozide) has an overall insect control spectrum similar to that of RH-5849 but with accentuated soil systemic efficacy against scarabacid beetle larvae, cutworms and webworms. RH-2485 (methoxy-fenozide) is more potent than tebufenozide against lepidopteran pests of cotton, maize and other major agricultural crops.
Methoxyfenozide induces an immediate and fatal moult in S. littoralis when added to the diet of 2nd and 4th instar larvae at 1 ppm and to that of 6th instar larvae at 0.001 ppm concentration. Ten times lower doses fed to the larvae continuously allow an apparently normal larval development that is terminated by a supernumeracy larval moult.
The other effects of methoxyfenozide include death during metamorphosis and impaired fertility of emerged adults. The number of progeny is reduced even with low doses, e.g. insects fed 0.0001 ppm since 2nd, 4th and 6th instars produce 72, 62, and 22 per cent, respectively, less progeny than the controls.
The ecdysone agonists have been tested in larvae and adults of more than 16 different insect orders, but these compounds have produced lethal effects mostly in lepidopteran, dipteran and coleopteran larvae. The high binding affinity of tebufenozide and methoxyfenozide to proteins in nuclear extracts of lepidopteran cells is correlated with their selective action on lepidopteran insects.
By contrast, the ecdysteroid receptors of coleopteran insects bind tebufenozide with low affinity. This difference thereby explains the specificity of this compound for lepidopteran insects. Ecdysone agonists affect all larval stages but the effect induced depends on when the insect ingests or is treated with the compounds during the time of application within a stadium.
If treatment occurs early in an instar, an immediate lethal molt is induced, but if the insect is treated towards the end of an instar, first a normal moult will occur, which is then followed by the lethal moult. In adult stage insects, egg production and spermatogenesis may be adversely affected by exposure to the ecdysone agonists.
Sclerotization Disruptors:
Sclerotization is a complex process used by insects to confer stability and mechanical versatility to their cuticular exoskeletons and certain other proteinaceous structures. Inhibitors of sclerotization may disrupt the metabolism and/or deposition of phenolic compounds, proteins or other components that participate in cuticular stabilization mechanism.
The only commercially available sclerotization inhibitor is MON 0585 developed by Monsanto. It is a di-tertiary butyl alcohol compound which is highly toxic to mosquitoes and other dipterous insects. It causes mortality at the time of pupation and dead pupae are white instead of tan colour because of failure of the organism to harden the pupal skin.
Another group of compounds with capacity to inhibit sclerotization are inhibitors of the enzyme 3, 4-dihydroxy-phenyl-alanine decarboxylase (DDC). DDC inhibitors like a-methyl DOPA cause mortality in dipteran larvae at the time of moulting. Accelerators of sclerotization process also exert a toxic effect on insects.
Cyromazine, a substituted diaminotriazine produces necrotic lesions in the cuticle of blowfly and stiffens housefly larval cuticle by inserting an extra layer between the endo-and exocuticle, causing rod like puparia. The cuticle of Manduca sexta (Johannsen) is unable to expand following treatment with cyromazine.