Anti cancer properties of Estriol
I discussed how the Estriol in Biest, the oestrogen most of my menopausal patients receive, has major benefits to women, yesterday in my blog. Here is some other interesting research into the anticancer properties of Estriol. The biochemistry is very technical, so read the last paragraph to get the gist of the study.
Mol Endocrinol. 1997 Nov;11(12):1868-78.
Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol.
1Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Estriol acts as a weak estrogen when administered in a single dose into immature or ovariectomized laboratory animals, but produces full estrogenic responses upon chronic administration. However, when estriol is injected together with estradiol it acts as an antiestrogen. We studied the dual agonist/antagonist properties of estriol, using recombinant human estrogen receptor (hER) in ligand-binding assay, cell-free transcription assay, electrophoretic mobility shift assay with cVitII estrogen response element (ERE), and ERE-Sepharose chromatography. We show that the weak estrogenic activity of estriol results from impaired hER-ERE interaction. The antiestrogenic activity of estriol was demonstrated in a cell-free transcription assay where it reduced estradiol-dependent transcription in a dose-dependent manner. Estriol interfered with estradiol-induced positive cooperative binding and receptor dimerization, and binding of hER complexes to ERE. These effects of estriol were maximal at a 10-fold molar excess over estradiol; under these conditions estradiol-dependent transcription was decreased by 85%, although [3H]estradiol binding was reduced by only 50%. We propose that when hER, estradiol, and estriol are coequilibrated, several receptor species are formed: unliganded hER monomers and dimers; estradiol-hER monomers and dimers, estriol-hER monomers and dimers; and presumably mixed estradiol-estriol dimers. Since estrogen-hER complexes bind cooperatively to ERE sequences, the concentrations of transcriptionally active complexes (estriol- and estradiol-hER dimers) are reduced to low levels that fail to bind cooperatively with ERE and initiate transcription.
We discuss our results in relation to the massive estriol production during pregnancy and to the “Estriol Hypothesis” on the protective role for estriol in opposing carcinogenic effects of estradiol.