Hormones, mimics

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine system because of the abihty of these chemicals to mimic or block endogenous hormones, or otherwise interfere with the normal function of the endocrine system. Chemicals with this type of activity are most commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995 Livingston 1978 Mayr et al. 1992). 

Ketone (31) was used in a synthesis of juvabione (32) an insect hormone mimic produced by conifers. 

Stable in acidic, neutral and basic aqueous solutions Pale yellowish solid, faint characteristic odor Flash point 119°C (Pensky-Martens closed tester) Pyriproxyfen is an insect growth regulator which acts both as an ovacide and as an inhibitor of development (juvenile hormone mimic) against white flies, scale, and psylla. The specificity of pyriproxyfen, and its low mammalian toxicity, allow for some variation in application timing. For example, the lack of toxicity to bees allows pyriproxyfen to be applied during bloom on apple trees, and its low mammalian toxicity allows for a very short pre-harvest interval on citrus The residue definition is for pyriproxyfen alone... 

Andrew Regan was born in Rawtenstall, Lancashire and studied at the University of Cambridge, where he obtained his BA in 1981 (MA 1985), and his PhD in 1984, under the supervision of Professor Jim Staunton. From 1984-1985 he held an SERC-NATO Research Fellowship at Columbia University in the laboratories of Professor Gilbert Stork. He returned to the UK in 1985 to a lectureship in organic chemistry at the University of Kent at Canterbury, and since 1990 has been a lecturer in the Department of Chemistry at the University of Manchester. His research interests include the synthesis of phosphinic-acid hormone mimics, simplified macrolide antibiotics and anti-tumour compounds, stereoselective methodology, and the use of enzymes in synthesis. 

Existing tests and bioassays of very distinct types have been proposed by different international bodies for the identification of hormonal mimics/antagonists, in an effort to assess the risk of exposure to... 

Era of Hormone Mimics and Pheromones, Rebirth of Botanical Insecticide ... 

The pest mosquito Aedes nigromacul Ls of the vast San Joaquin valley of California went resistant to organochlorines by 1951, to parathion by 1960, to fenthion by 1965, and to chlorpyrifos (Dursban) by 1970. At present reliance is placed on larvicidal oils, the juvenile-hormone mimic methoprene (Altosid) and the insect growth regulator diflubenzuron (Dimilin), — and on better management of surplus irrigation water. Residual sprays for housefly control, at first so spectacular with the organochlorines, had to move into the OP compounds, which were then knocked out in... 

The multiresistant strains now extant also show a certain cross-tolerance, but not resistance, to the third-generation insecticides such as the juvenile-hormone mimics and other so-called insect growth regulators, as was found in strains of the housefly, flour beetle and tobacco budworm. Resistance to the JH mimic methoprene and Monsanto-585 has been induced by laboratory selection of Culex taxsalis (28) and Culex pipiens (29), and to Monsanto-585 in Culex quinquefasstatus (30). Whatever insect or IGR is chosen, the result of exposure to selective doses in successive generations is usually the development of resistance, repeating our previous experience with chemosterilants, and the... 

An example of increasing the efficiency by decreasing the flow rate is shown on a pellicular silica gel column in Figure 6-5a. (This figure was shown previously as Fig. 4-15.) This is the separation of a cis and trans isomer of synthetically prepared juvenile hormone mimics which are separated in the normal-phase mode. (Juvenile hormone mimics are used to stop or retard the maturation process of insects and, hopefully, control the insect population.) The presence of benzene is probably residue from the reaction solvent. At 2 mL/min the first peak corresponds to 5000 plates and the last peak corresponds to 2300 plates. By lowering the flow rate to 0.5 mL/min, there is a corresponding increase in efficiency in the separation. With the additional efficiency at the slower flow rate, it is possible to observe a small, additional shoulder (peak) under the first peak. However this was done at the expense of increased time (a factor of 4). 

FIGURE 6-5. Effect of flow rate upon the separation, (a) Normal-phase separation of juvenile hormone mimics. Column Corasil II (silica), 2 mm x 183 cm. Mobile phase ethyl ether/hexane (1/199). Detector UV Flow rate 2.0 mL/min and 0.5 mL/ min. (b) GPC separation of phthalates. Column 100 A juStyragel, 8 mm x 30 cm. Mobile phase tetrahydrofuran. Detector RI Sample dioctylphthalates dibutylph-thalate, diethylphthalate, and dimethylphthalate. Flow rate shown on chromatogram. 

The existence of a cytosolic epoxide hydrolase was first indicated by its ability to hydrolyze analogs of insect juvenile hormone not readily hydrolyzed by microsomal epoxide hydrolase. Subsequent studies demonstrated a unique cytosolic enzyme catalytically and structurally distinct from the microsomal enzyme. It appears probable that the cytosolic enzyme is peroxisomal in origin. Both enzymes are broadly nonspecific and have many substrates in common. It is clear, however, that many substrates hydrolyzed well by cytosolic epoxide hydrolase are hydrolyzed poorly by microsomal epoxide hydrolase and vice versa. For example, l-(4 -ethylphenoxy)-3,7-dimethy I -6,7-epoxy-//7//i,v-2-octene, a substituted geranyl epoxide insect juvenile hormone mimic, is hydrolyzed 10 times more rapidly by the cytosolic enzyme than by the microsomal one. In any series, such as the substituted styrene oxides, the trans configuration is hydrolyzed more rapidly by the cytosolic epoxide hydrolase than is the cis isomer. At the same time, it should remembered that in this and other series,... 

Synthetic pyrethroids, avermectins, juvenile hormone mimics, biological pesticides 1985- Genetically engineered organisms... 

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