Interaction of Δ5-Androstene-3β,17β-diol with Estradiol and Dihydrotestosterone Receptors in Human Myometrial and Mammary Cancer Tissue1

Abstract

Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.