Characterisation of gestodene binding to the oestrogen receptor in human malignant breast tissue

Gestodene, a new synthetic progestogen, binds to progesterone receptor (PR) derived from normal breast, endometrium and both normal and diseased liver with an affinity 8-10 times higher than that of the natural ligand. PR in malignant breast could not be quantified on account of the binding of gestodene to oestrogen receptor (ER) in that tissue. Sucrose density ultracentrifugation using 3H-oestradiol and 3H-gestodene in normal and malignant breast demonstrated that the gestodene-ER complex in addition to exhibiting the 4S and 5S peaks showed an additional peak which sedimented at 2.9-3.15. Dissociation kinetics of gestodene from ER which was either heat-activated or molybdate-stabilised were comparable to the triphenylethylene class of antioestrogens in that the rate of dissociation, unlike that of oestradiol from ER, was unaffected by these treatments. The binding of ER-gestodene to DNA-cellulose was also investigated and was found to be approximately 30% less than that of ER-oestradiol.