Comparative affinity of steroidal and non-steroidal antioestrogens, cholesterol derivatives and compounds with a dialkylamino side chain for the rat liver antioestrogen binding site.
Steroidal and non-steroidal antioestrogens, steroidal compounds with (disubstituted) dialkyl amino side chain, cholesterol derivatives, histaminic and (anti)-progestational compounds were tested for their ability to compete with [3H]tamoxifen for the specific antioestrogen binding site (AEBS) in the post-mitochondrial fraction of rat liver homogenates. Relative binding affinity was highest for compounds with diethylamino or pyrrolidino ethoxy side chains. Affinity decreased with shortening of this side chain. No connection could be established between the carbon backbone of the compound and affinity, except for the presence of (sometimes aromatic) ring structures. Steroidal ring structures do not seem to be necessary for binding. The cholesterol derivatives, tested in our laboratory, showed very little affinity for the rat liver AEBS. Histamine, melatonin and the (anti)-progestational compounds showed no affinity for the AEBS; and we therefore conclude that the AEBS is not identical to receptors for these compounds. Results of these experiments could be useful in other investigations on the development of resistance of breast cancer to antioestrogens.
van den Koedijk
C D
CD
Department of Pharmacy, Utrecht University, The Netherlands.
Vis van Heemst
C
C
Elsendoorn
G M
GM
Thijssen
J H
JH
Blankenstein
M A
MA
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002784:Cholesterol / Q000378:metabolism*; D004351:Drug Resistance; D004965:Estrogen Antagonists / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism
D004965:Estrogen Antagonists; D011955:Receptors, Drug; D011960:Receptors, Estrogen; D013629:Tamoxifen; D002784:Cholesterol