The in vitro interference of some gestagens with the binding of 3H-17-beta-oestradiol to cytosol specific receptors was investigated with a view to elucidating the mechanism of action of progestins in the treatment of human hormone-dependent breast cancer. A decrease (up to 85%) of oestradiol binding capacity was observed with high concentrations of progesterone, clogestone and medrogestone. These findings are in good agreement with those previously obtained by the same progestins in our laboratory on rat uterine estrogen receptors in vitro or in vivo. These results provide the support for the hypothesis that the mode of action of progestins in the therapy of mammary and perhaps uterine carcinomas is to some extent related to the inhibition of oestradiol binding to cytosol specific receptors.
PIP: For the purpose of explaining the mechanism of action of progestins in the treatment of human hormone-dependent breast cancer, interference of some progestins with the binding of radioactive 17beta-estradiol to its specific receptors in a cytosol substrate in vitro was studied. A decrease of up to 85% in the binding capacity of estradiol was observed with high concentrations of progesterone, clogestone, and medrogestone. These findings appear to confirm those obtained by the same authors using the same progestins on rat uterine estrogen receptors in vitro and in vivo, and support the hypothesis that the mechanism of action of progestins in the treatment of breast and possibly uterine cardinoma is to some extent related to the inhibition of estradiol binding to its specific receptors, thereby inhibiting the formation of the estrogen-receptor system which is the cause of cell growth in such tumors. This would also explain the greater frequency of successful treatment when using higher doses of progestins.