Estrogen Receptor Antagonists Complexes

Fig. 8.3 Yeast-based screen for agonists or antagonists of the human estrogen receptor. The hormone estrogen (estradiol) binds to the estrogen receptor which is expressed from a gene driven by the PGK promoter. The hormone-receptor complex binds to an estrogen-responsive element (ERE) that controls the expression of the p-galactosidase reporter gene. The assay measures the activity of the enzyme using a substrate that forms a colored product on conversion.

Fig. 10.12 Ferrocifen derivative (Z isomer), 3, docked at the estrogen protein receptor site and shows the organometallic complex inside the antagonist binding site of the estrogen receptor.

The mechanisms of action of steroid hormones on lymphoid, mammary, and prostatic cancer have been partially clarified. Specific cell surface receptors have been identified for estrogen, progesterone, corticosteroids, and androgens in neoplastic cells in these tissues. As in normal cells, steroid hormones also form an intracellular steroid-receptor complex that ultimately binds directly to nuclear proteins associated with DNA to activate transcription of a broad range of cellular genes involved in cell growth and proliferation (see Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists). 

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