Steroid binding to the cytosolic estrogen receptor from rat uterus. influence of the orientation of substituents in the 17-position of the 8β- and 8α-series

The exact chemical and sterical requirements in the 17-position of 8β- and 8α-estrogens for an effective binding to the cytosolic receptor of immature rat uterus were investigated by competition experiments under non-equilibrium conditions. Oxygen or nitrogen functions with free electron pairs seem to be of essential importance in the 17-position. In contrast to 17α-methyl-, -vinyl- or -ethinyl-substituents a 17α-ethyl group strongly disturbs receptor binding. Also the introduction of a quasi equatorial allene or a 17β-ethinyl group reduces receptor binding. In comparison to the 8β -estrogens, the 8α-derivatives always showed lower, but still significant receptor binding and similar response to changes of substituents in the 17-position.