Differential induction of pS2 and cathepsin D mRNAs by structurally altered estrogens.

The influence of structural alterations to the estradiol-17 beta (E2) molecule on the induction of pS2 and Cathepsin D (Cath D) mRNAs has been examined by Northern analysis of RNA extracted from MCF-7 cells. Exposure of cultures to estratriene did not affect the level of expression of these estrogen-responsive genes. Addition of one hydroxyl group to estratriene at either of the hydroxylated positions of E2 (3-phenolic or 17 beta) yielded monohydroxyestrogens which stimulated the synthesis of Cath D and pS2 mRNAs to a level comparable to that induced by 10(-10) M E2 and displayed a decrease in activity at the higher concentrations (10(-8) - 10(-7) M) similar to that of the parent estrogen. Both of these genes were induced maximally by estrogens with D-ring alterations. Movement of the phenolic hydroxyl group of E2 to other positions on the A-ring yielded ligands which were highly discriminatory in the induction of these messages. 1-Hydroxyestratrien-17 beta-ol was capable of stimulating maximal synthesis of both pS2 and Cath D mRNAs when added to cultures of MCF-7 cells at a concentration of 10(-8) M. Placement of the phenolic hydroxyl at position 4 greatly diminished the induction of these two estrogen-responsive genes. On the other hand, positioning the A-ring hydroxyl group on carbon 2 yielded a ligand which brought about the induction of one gene (pS2) but was marginally effective in the induction of Cath D mRNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)