T Nation

Question for Bill Roberts


Hi Bill,

I was wondering if you have ever read/seen/heard about the possibility of two ligands binding to each portion of the steroid receptor dimer and forming some 'hybrid heterozygous dimer' that would recruit different regulators than either of the homologous dimers would? I haven't seen anything to affirm this idea, but I also am not aware of anything to disprove it....

I am looking at Beta estrogen receptor distribution in various areas of the brain and was curious if both 3 beta diol and estradiol could bind at the same time to one half of the receptor dimer...

Any help you could offer would be much appreciated, as I respect your opinion on these matters more than anyone.


That is a matter that seems to hardly ever be brought up. Yet it would seem clearly important.

I actually do not know much about it. You are right that two different ligands may be bound and that this can result in a different effect than the same ligand being bound, but precisely how this relates to the actions of the selective estrogen receptor modulators, or the actions of say estriol, I don't know. I expect it it is a relevant additional mechanism to their partial estrogen antagonism. Namely, by changing the effects of estradiol binding to the other part, relative to what would have happened had the dimer been homogenous for estradiol.

The only paper I know on it is http://jme.endocrinology-journals.org/cgi/content/full/38/5/569

Hopefully it will be helpful.