ESTROGENIC AND PROGESTAGENIC ACTIVITIES OF PHYSIOLOGICAL AND SYNTHETIC ANDROGENS, AS MEASURED BY IN-VITRO BIOASSAYS

Estrogenic activities of testosterone (T) and 5 alpha-dihydrotestoster one (DHT) were detected and measured by using their specific stimulato ry effects on alkaline phosphatase (AP) activity in human endometrial adenocarcinoma cells of the Ishikawa Var-1 line. These two physiologic androgens were able to induce, at mu M concentrations, estrogenic eff ect believed to be mediated by the estrogen receptor (ER) since the an tiestrogens ICI-164384 and 4-hydroxytamoxifen (OHTam), but not the ant iandrogens hydroxyflutamide (OHFl) or cyproterone acetate (CPA), rever sed that effect. By using another in vitro bioassay, based on the prog estin-specific stimulation of AP activity in cells of the T47D human b reast cancer line, progestagenic activity was detected and measured in T, DHT and three synthetic androgens: nandrolone (19-nortestosterone) , 7 alpha-methyl 19-nortestosterone (MENT) and mibolerone (7 alpha,17 alpha-dimethyl 19-nortestosterone)(DMNT). While progestagenic effects of T and DHT required relatively high concentrations (mu M levels), th e synthetic androgens stimulated AP activity at nM or pM levels. These effects seem to be mediated by the progesterone receptor (PR), since they are completely abolished by the antiprogestins RU-486, ZK-98299 a nd ZK-112993, but not by the antiandrogen OHFl. These simple in vitro bioassays, expressing biological effects of the test compounds in huma n cells in culture, revealed dual or multiple hormonal activities coex isting in a single compound and provide quantitative information of co nsiderable pharmacological importance concerning the complex actions o f drugs.