Ecdysteroid effect

From these studies, some patterns of effect potentially mediated by the endocrine system have been observed. These include the accumulation of vitellogenin in ticks [50-52] and accelerated ovarian development in beetles and ticks [51, 53]. Different researchers have attributed these effects to a range of different mechanisms, including induced excitation of neurosecretory cells releasing juvenile hormone [50], and ecdysteroid disruption either by blocking the neuropeptide itself or at the epidermal site of synthesis [51]. Other researchers have not corroborated these results and have even found contradictory effects, e.g., suppressed ovarian development [52], Therefore at present for SPs, there is no clear evidence for adverse population-relevant effects with an underlying endocrine mode of action. 

Juvenile hormone (JH) regulates both vitellogenesis and pheromone production in some insect species (Tillman et al., 1999). In some Diptera, including the housefly, ovarian-produced ecdysteroids are involved in regulating vitellogenesis (Hagedom, 1985 Adams et al., 1997) at the transcriptional level (Martin et al., 2001). Because ovariectomy abolished sex pheromone production while alletectomy (which abolishes JH production) had no effect on pheromone production (Blomquist et al., 1992), it was therefore hypothesized that an ecdysteroid, and not JH,... 

HE into ovariectomized insects over several days resulted in as much (Z)-9-tricosene produced as in intact control females. Application of JH or JH analogs alone or in combination with ecdysteroids had no effect on pheromone production, confirming that JH does not have a role in regulating housefly pheromone production (Blomquist et al 1992). 

The purpose of this review is to summarise the effects, modes of action, structural diversity and biological activity of ecdysteroids and to show how ecdysteroid QSAR and molecular modelling are being applied in agriculture and medicine. 

Two main hypotheses have been put forward to account for the occurrence of ecdysteroids in the plant world. The first is that PEs have a hormonal role within the plant, but there is very little hard evidence in support of this hypothesis (reviewed in [26]). Alternatively, PEs participate in the defence of plants against non-adapted phytophagous invertebrates. Deterrent effects of 20E on non-adapted insect species are... 

In addition to the actions mediated by intracellular receptors, steroid hormones also demonstrate certain rapid (occurring within seconds) actions, which appear to be mediated by membrane effects/receptors this is true for vertebrate [114] and invertebrate [115] steroids. One presumes that the SAR studies for ecdysteroids which have been performed to date are predominantly determined by interaction of ecdysteroids with nuclear receptors, but one should bear in mind that in certain assay systems the... 

Lin et al. [149] have recently reported the synthesis of 2-(4,5-dimethoxy-2-nitrobenzyl)-20-hydroxyecdysone (6-6), which itself has a very low affinity for ecdysteroid receptors expressed in mammalian 293T cells, but can be photolysed at 348 nm to release 20E, which then activates the receptor-regulated reporter gene. With this system, it will be possible not only to control the temporal activation of transfected genes, but also their spatial activation. The authors recognise that the effectiveness of this system can be considerably improved in future by derivatising an ecdysteroid (poA or muA) which is more active in ecdysteroid-responsive mammalian cells. 

The effect of a few ecdysteroids and the BAHs, RH5849 and RH5992, on cell density of the cell lines Cl8+ and C18R were determined [194], All compounds had similar effects, but C18R was 10-100-fold less sensitive to the ecdysteroid analogues. It was not reported if these cell lines metabolise ecdysteroids. The activities with the Cl8+ cells were 20E (EC50 = 6 x 10 8M), Ino (4 x 10 7M), MaA (5 x 10 8M) and MuA (6 x 10 9 M). 

Although no SAR currently exist for the pharmacological effects of ecdysteroids on any vertebrate species, as these effects become more generally accepted, it will be necessary to conduct such studies to determine which are the most effective analogues to apply. 

Scheme 3). A clone of cells from the midge Cbironomus tentans was found to be resistant to the effects of ecdysteroids because they metabolized 20-hydroxyecdysone rapidly. The initial oxidation product was 20,26-dihydroxyecdysone, but this was oxidized further to 20-hydroxy-26-oxo-ecdysone (21). This aldehyde (21) then formed a tautomeric equilibrium mixture of two cyclic hemiacetals (22) and (23), which were separable, isolated, and their structures determined (Scheme 3) with the use of acetonides (Section 4.03.3.6).32 These are the first examples of ecdysteroids with side-chain hemiacetals. Although 20,26-dihydroxyecdysterone still... 

To date, interest in the ecdysteroids has focused primarily on their role in insect molting and metamorphosis and it is perhaps somewhat unfortunate that bioassays for ecdysteroid activity have been restricted almost exclusively to evaluating their effect on the molting process. It now appears probable that molting is just one of several important regulatory functions (e.g., embryogenesis, reproduction) performed by the ecdysteroids and that we are only just beginning to scratch the surface of an insect steroid system that is equally as complex as that in vertebrate species. 

---