Oestrogen activity

It is not certain that all the effects of DES can be ascribed to its oestrogenic activity (that is to say, directly related to its ability to bind to the oestrogen receptor), but it would appear from experience with this compound that rodent assays are able to detect the relevant toxicological effects. What then was the... 

Dodds, E.C. and Lawson, W. (1938). Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proceedings of the Royal Society of London, Series B Biological Sciences 125, 222-232. 

Dodds, E.C., Fitzgerald, M.E.H., and Lawson, W. (1937). Oestrogenic activity of some hydrocarbon derivatives of ethylene. Nature 140, 772-772. 

Panter, G.H., Hutchinson, T.H., and Hurd, K.S. et al. (2006). Development of chronic tests for endocrine active chemicals—Part 1. An extended fish early-life stage test for oestrogenic active chemicals in the fathead minnow (Pimephales promelas). Aquatic Toxicology 77, 279-290. 

Besides these toxic effects, many studies showed the potential for oestrogenic activity of several sunscreen agents. These effects can be detected in vivo or at in vitro assays. The last are usually more sensitive than the former, concluding sometimes in an overestimation of the effects. Nevertheless, in vitro assays are faster and cheaper and allow a rapid screening of oestrogenic compounds. Therefore, a combination of different assays is recommended in order to have a wide spectrum of toxicity data that would allow performing a reliable risk assessment. 

For the last forty years, many reports have emerged on the hormone-like effects of chemical compounds such as pesticides and industrial chemicals upon wildlife and humans. The effects of these materials are believed to be either direct or indirect. Direct effects involve positive or negative interactions with the hormone receptors. Indirect effects may result when the synthesis of hormones or their receptors is altered, or the transport, metabolism, or elimination of hormones is modified in some way. The discovery of hormone-like properties of some compounds was made long after their release into the environment. It was shown soon after their introduction that aviation crop dusters handling DDT had low sperm counts and workers at a plant producing the insecticide kepone were reported to have low libido, sperm counts and to be impotent. Subsequently, experiments conducted in laboratory animals demonstrated unambiguously the oestrogenic activity of these pesticides. 9 refs. 

Clomiphene is a nonsteroidal agent with oestrogenic and anti-oestrogenic properties. The mechanism of action is not precisely clear, but it ultimately leads to the release of the pituitary gonadotropins FSH and LH. It stimulates ovulation in anovulatory or oligo-ovulatory women with adequate endogenous oestrogen activity and an intact hypothalamic-pituitary-ovarian axis. 

Panter G.H., R.S. Thompson, N. Betesord, and J.P. Sumpter (1999). Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity. Chemosphere 38 3579-3596. 

Allen, Y, Scott, A.P., Matthiesen, R, Haworth, S., Thain, J.E., Feist, S. (1999b). Survey of oestrogenic activity in United Kingdom waters and its effects on gonadal development of the flounder Platichthys flesus. Environmental Toxicology and Chemistry, 18 1791-1800. 

However, the binding affinities of 197,206 and 207 [0.3%, 0.1% and <0.01%, respectively, relative to oestradiol (100%)] for the oestrogen specific acceptor protein of the rat uterus suggest that a steric or an electronic effect, rather than metabolic instability, is responsible for the absence of oestrogenic activity in these compounds. But a clear answer cannot be given because biological data of the direct 6,6-dimethyl-6-carba-analogues are not known so far. 

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