Estrogen properties

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

As discussed in the Endocrine Effects section, endosulfan has shown weak estrogenic properties in some in vitro assays, but no such properties could be confirmed in studies in vivo. 

In discussing the enviromnental fate of technical DDT, the main issue is the persistence of p,p -DDT and its stable metabolites, although it should be bom in mind that certain other compounds— notably, o,p -DDT and p,p -DDD—also occur in the technical material and are released into the environment when it is used. The o,p isomer of DDT is neither very persistent nor very acutely toxic it does, however, have estrogenic properties (see Section 5.2.4). A factor favoring more rapid metabolism of the o,p isomer compared to the p,p isomer is the presence, on one of the benzene rings, of an unchlorinated para position, which is available for oxidative attack. p,p -DDD, the other major impurity of technical DDT, is the main component of technical DDD, which has been used as an insecticide in its own right (rhothane). p,p -DDD is also generated in the environment as a metabolite of p,p -DDT. In practice, the most abundant and widespread residues of DDT found in the environment have been p,p -DDE, p,p -DDT, and p,p -DDD. 

The estrogenic properties of isoflav-3-enes are well known and consequently, several derivatives of these chromene heterocycles have been the target of medicinal chemists. Varma and coworkers uncovered a useful enamine-mediated pathway to this class of compounds [142-144], Now the group has discovered a facile and general method for the MW-expedited synthesis of isoflav-3-enes substituted with basic moieties at the 2-position (Scheme 6.42) [145], These promising results are especially appealing in view of the convergent one-pot approach to 2-substituted isoflav-3-enes... 

Trioxifene is an older SERM with low estrogenic properties and a higher affinity for ER than tamoxifen. It has shown an unfavorable safety profile in clinical studies of women with breast cancer (leukopenia in 41% of patients, nausea in 31%) (Witte et al. 1986), which is why, in addition to its response rates being no better than in tamoxifen (Lee et al. 1986), its clinical development has been cancelled. 

The estrogenicity of BPA has been well studied and documented for many years. To the best of our knowledge, the first report of the estrogenic properties of BPA was published by Dodds and Lawson [23] in 1936, as mentioned above. Later, Reid and Wilson [33] confirmed... 

Cochran RC, Wedow MA. 1984. Chlordecone lacks estrogenic properties in the male rat. Toxicol Appl Pharmacol 76 519-525. 

Nonylphenol has recently been shown to have estrogenic properties, triggering mitotic activity in rat endometrium and cell proliferation in estrogen-sensitive tumor cells. Potential toxicity to humans who may be exposed to nonylphenol through leaching of plastics has not been determined. 

N.A. Sitosterol, tannins, saponins, tribulusamide A and B, n -1 mn.v-fcru loy 1 tyram i nc, terrestriamide, n -1 runs-a mm aroy Ityram i nc.174 Estrogenic properties, antiandrogenic action, reduce benign prostate hyperlasia (BPH). 

Effects on sexual behaviour should be considered adverse. Testing of sexual behaviour is not usually available and not warranted in all cases, but should be considered for those agents that cause neurotoxicity and those that have agonistic or antagonistic adrenergic or estrogenic properties. 

They also reported that on the basis of a review of data on over 2000 chemicals that have been tested in various in vitro and/or in vivo assays, all chemicals showing estrogenic properties contained a ring structure. All except five of the ring structures were aromatic (the exceptions being four steroids and the pesticide kepone). Table 18.1 illustrates the presence of these features in various categories of chemicals. 

Gagne, F. and Blaise, C. (1998b) Estrogenic properties of municipal and industrial wastewaters evaluated with a rapid and sensitive chemoluminescent in situ hybridization assay (CISH) in rainbow trout hepatocytes, Aquatic Toxicology 44 (1), 83-91. 

Vessieres A, Top S, Pigeon P, Hillard EA, Boubeker L, Spera D, Jaouen G (2005) Modification of the estrogenic properties of diphenols by the incorporation of ferrocene. Generation of antiproliferative effects in vitro. J Med Chem 48 3937-3940... 

Disturbance of reproduction. Quite a number of allelochemicals are known to influence the reproductive system of animals, which ultimately reduces their fitness and numbers. Antihormonal effects could be achieved by mimicking the structure of sexual hormones. These effects are not known for alkaloids yet, but have been confirmed for other natural products. Estrogenic properties have been reported for coumarins, which di-... 

In the last few years, special attention has also been paid to the exposure of humans to bisphenol A (4 -dihydroxy-2,2-diphenyl, BPA Fig. 7.1), well-known for its estrogenic properties. BPA [28] is commonly used as an industrial plasticizer and is found in paints, flame retardants, unsaturated polyester resins, plastic food packaging, containers for water, infant feeding bottles, and foils used for food storage. Several studies have confirmed the presence of BPA, at a detectable level, in a wide variety of food containers [29-31]. Views on the potential danger... 

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