Estrogens mechanisms

A general overview of endocrine disrupters and estrogens mechanism(s)... 

Gustafsson, J. A. 1999. Estrogen receptor beta a new dimension in estrogen mechanism of action. J. Endocrinol. 763 379-83. 

In addition, several progestins have been used in the absence of estrogens for purposes of contraception. It is clear that they owe their efficacy, which is not as high as that of the combination or sequential treatments, to some mechanism other than inhibition of ovulation. These are not yet represented by marketed entities for that indication. 

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%. 

Classical examples of this type of reaction are the various dimethylaminobenz-aldehyde reagents (q.v.) and vanillin-acid reagents, of which one, the vanillin-phosphoric acid reagent, is already included in Volume 1 a. The aldol condensation of estrogens is an example for the reaction mechanism (cf. Chapter 2, Table 6). According to Maiowan indole derivatives react in a similar manner [1]. Longo has postulated that catechins yield intensely colored triphenylmethane dyes [2]. 

In addition to the foregoing, three further examples in this list (numbers 5-7) deserve consideration. These are (5) interaction of endocrine disrupters with the estrogen receptor, (6) the action of uncouplers of oxidative phosphorylation, and (7) mechanisms of oxidative stress. Until now only the first is well represented by biomarker assays that have been employed in ecotoxicology. 

Particular attention is given to the development of new mechanistic biomarker assays and bioassays that can be used as indices of the toxicity of mixtures. These biomarker assays are typically based on toxic mechanisms such as brain acetylcholinesterase inhibition, vitamin K antagonism, thyroxin antagonism, Ah-receptor-mediated toxicity, and interaction with the estrogenic receptor. They can give integrative measures of the toxicity of mixtures of compounds where the components of the mixture share the same mode of action. They can also give evidence of potentiation as well as additive toxicity. 

Filby, A.L., Thorpe, K.L., Maack, G. et al. (2007b). Gene expression profiles revealing the mechanisms of anti-androgen and estrogen-induced feminization in fish. Aquatic... 

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