Relative binding affinity of androstane and C-19-nor-androstane-steroids for the estradiol-receptor in human myometrial and mammary cancer tissue.
The relative binding affinity of several androstane- and C-19-nor-androstane-compounds for the estradiol (E2)-receptor in human myometrial and mammary cancer tissue was studied. High speed cytosol was incubated with tritiated E2 alone as well as in the presence of increasing amounts of the compound to be tested. The highest affinity is found for steroids with two hydroxyl-groups at C-3 and C-17 in the beta-position and a double bond at C-4-5 or C-5-6. Saturation of the A-ring decreases the affinity: 5alpha-compounds have less affinity, 5-beta-compounds have less affinity; 5beta-compounds hardly any affinity. The presence of a hydroxyl-group in the 3alpha, 11beta or 16beta-position decreases the affinity, as dose a 3-oxo or 17-oxo-group. Removal of the C-19-methyl-group facilitates the binding. This data led to the concept that flatness of the A-ring in respect to the B-ring of the steroid molecule is a principal requirement for binding to the E2-receptor. The rank order of RBA is identical in myometrium and in mammary cancer tissue, indicating that estrogen-receptors are at least highly similar in both target tissues.
D015113:Androstane-3,17-diol / Q000378:metabolism; D000731:Androstanes / Q000378:metabolism*; D000734:Androstenediols / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D009215:Myometrium; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism*
D000731:Androstanes; D000734:Androstenediols; D011960:Receptors, Estrogen; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol