Potent estrogens show cell growth stimulatory activity at exceedingly low concentrations. It is rare to have a functional assay system that can operate over a concentration range of 10 millionfold. There are some common structural motifs among compounds with estrogenic activity. Most compounds that have estrogenic activity are phenols. Thus, the most rudimentary structural motif that elicits estrogenic activity is a phenol that is relatively unhindered at the ortho positions, but then contains a rather bulky, hydrophobic structure attached to the meta or para positions.
Estrogens tend to be rather hydrophobic.
As the structural mimicry of an estrogen deviates more and more from that of estradiol, some estrogenic activity is generally ensured by having the compound be hydrophobic. It is perhaps a conspiracy of nature that hydrophobic compounds, particularly those resistant to metabolic degradation such as polychlorinated materials or those with highly branched alkyl substituents, persist in the environment and may undergo bioconcentration, thereby amplifying the potential exposure of these agents to those at the end of food chains. Regardless of the molecular details of ligand receptor interaction or the transduction of the signal of receptor activation into response that are responsible for this fact, the consequences of the structural diversity of estrogens in terms of human and animal health need to be soberly evaluated. Some effects of estrogens in unwanted places, such as impurities in pH indicator dyes used in cell culture media or components that leach out of polycarbonate media bottles, are simply nuisances that confound the results of cell culture experiments. These compounds, to which humans are exposed in large doses through the normal intake of healthy foodstuffs, are generally compounds of low potency, and their net effect on the endogenous human endocrine system may actually be that of estrogen antagonism.