EFFECT OF A-RING ISOMERS OF ESTRADIOL-17-BETA ON GENE-PRODUCTS IN MCF-7 CELLS

Two-dimensional polyacrylamide gel-electrophoresis analysis of in vitro translation products from extracted cellular mRNAs was utilized to examine the effect of A-ring isomers of estradiol (E(2)) on the synthesis of proteins involved in the response of MCF-7 cells to estrogens. An 8 h pulse with 10(-8) M E(2) showed II polypeptides of interest, 9 displayed a transitent increase in mRNA accumulation and 2 showed a temporary decreased level in the presence of this hormone. A distinct set of 2 mRNAs displayed increased amounts only after a 24h E(2) pulse. Position of the A-ring hydroxyl group on the estratrien-17 beta-ol moiety had a discriminatory effect on the mRNAs for the II polypeptides responsive to E(2). The accumulation of three mRNAs (A, C, and E) were increased by the 3 A-ring isomers (1-, 2-, and 4-hydroxyestratrien-17 beta-ol) to a degree comparable to that brought about by E(2). One mRNA (H) was decreased by all estrogens. The pattern of responses depicted in the remaining 7 polypeptides was different depending on the position of the A-ring hydroxyl group of the estrogen. Subtle changes in the structure of E(2) appear to attenuate the ability of this natural ligand to regulate certain estrogen responsive genes and not others. This phenomenon may be related to the interaction of TAF-2 in ligand bound receptor with the various regulators in the promoter region of specific estrogen responsive genes.