Evidence for a novel binding site for the synthetic progestogen, gestodene on oestrogen receptor in human malignant tissue.

The binding of the synthetic progestogen, 17 alpha-ethinyl-13 beta-ethyl-17 beta-hydroxy-4,15-gonadiene-3-one (gestodene) to estrogen receptor (ER) in malignant breast disease is refractory to competition by excess amounts of estra-1,3,5 (10)-triene-3,17 beta-diol (estradiol, E2) or tamoxifen, whereas gestodene in excess amounts can reduce the E2 binding sites by 31-44% and increase the Ka 2-3 times. Given the close similarity of the number of binding sites measured by E2 or gestodene and the similarity of dissociation constants, we propose that in the already altered ER of the malignant human breast there is another binding site for gestodene which closely approximates in number and affinity the binding site for E2, and that gestodene itself is capable of bringing about a configurational change which greatly reduces the binding of E2 to ER without completely abolishing it.