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Stimulation of transcription of reporter genes by the progesterone receptor (PR) was inhibited in transfected HeLa cells by co-expressing the estrogen receptor (ER) in an ER-dose- and estrogen-dependent manner. Both the N-terminal A/B region and the hormone binding domain of ER were involved in this inhibition, which was antagonized by antiestrogens and did not appear to involve direct interaction between ER and either reporter gene or PR. ER expression also inhibited activation by the glucocorticoid receptor (GR), and both PR and GR expression inhibited activation by ER, albeit to a lower extent. Similar transcriptional interference was observed between the endogenous PR and ER present in T47D and MCF-7 breast cancer cells transfected with an ER reporter gene. Moreover, transcription of the resident estrogen-induced pS2 gene was partially inhibited by exposing MCF-7 cells to progestins or glucocorticoids. We propose that these observations reflect competition for a functionally limiting transcription factor(s).

We have previously reported the presence of a hormone-inducible transcriptional activation function (TAF-2) within the region of the estrogen receptor (ER) that contains the hormone binding domain. We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells. By analyzing the ability of TAF-1, TAF-2, and the GAL4 and VP16 acidic activating domains (AADs) to homosynergize and heterosynergize with one another and with the factor binding to the upstream element (UE) of the adenovirus 2 major late promoter, we show that the activation properties of TAF-1 and TAF-2 are different and distinct from those of AADs, in agreement with the absence of acidic amino acid stretches in TAF-1 and TAF-2.