Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties

Allylestrenol (17 alpha-allyl-17 beta-hydroxy-4-estren) is an orally active progestagen of the 19-nortestosterone series resembling progesterone since it has no detectable androgenic activity in animal studies and in the human. In the present study, the affinity of its 3-keto metabolite for the transformed progesterone receptor in intact MCF-7 cells was about twice that of progesterone and cyproterone acetate and about 2-3 times less than that of medroxyprogesterone acetate and norethisterone, reflecting the known progestational activity of allylestrenol. The affinity of 3-ketoallylestrenol for the transformed androgen receptor in intact MCF-7 cells was weak (like other progestagens lacking androgenic activity or possessing anti-androgenic activity) and lower than that of weakly androgenic progestagens. On the other hand, the relatively high affinity of 3-keto-allylestrenol for the non-transformed androgen receptor at 4 degrees C in the cytosol fraction did not reflect the known lack of androgenic activity of allylestrenol. Thus competitive studies carried out with transformed receptor complexes in intact cells at 37 degrees C and non-transformed complexes in cytosol distinguish progestagen with weak androgenic activity (e.g. norethisterone) from those displaying no androgenic activity or possessing anti-androgenic activity (e.g. 3-keto-allylestrenol, progesterone, cyproterone acetate and spironolactone).