Gene regulation by steroid hormones is accomplished by a variety of different mechanisms all involving the hormone receptors but leading to induction or repression of particular genes depending on the cell type and on the sequence context of the genes regulatory region. Induction of the mouse mamma tumour virus (MMTV) promoter requires binding of the hormone receptor to the hormone responsive element (HRE) of the long terminal repeat region that is precisely organized in a phased nucleosome. Following receptor binding, changes in chromatin structure are detected that correlate with binding of transcription factors, including nuclear factor I (NFI), to the MMTV promoter. However, NFI acts as a basal transcription factor on the MMTV promoter and does not cooperate with the hormone receptors in terms of binding to free DNA. Moreover, promoters lacking the NFI binding site are still responsive to hormone stimulation in vivo and in vitro. This effect is mediated by two degenerated octamer motifs located immediately upstream of the TATA box, that together bind OTF-1 (Oct-1, NFIII) with similar affinity as the octamer consensus. In transfection experiments, mutation of these octamer motifs interferes with the hormonal response of the MMTV promoter. In vitro, these mutations do not influence basal transcription, but completely abolish the stimulatory effect of purified progesterone receptor. Progesterone receptor bound to the HRE facilitates binding of OTF-1 to the two octamer motifs. Thus, OTF-1 is a natural mediator of progesterone induction of the MMTV promoter and acts through cooperation with the hormone receptor for binding to DNA. On the other side of the response spectrum, glucocorticoids inhibit expression of various genes including the gene for a-subunit of the corionic gonadotrpins and the collagenase gene. The effect on the a-subunit gene is due to a competition between the glucocorticoid receptor (GR) and the protein mediating cAMP induction, CREB, for binding to overlapping sequences in the promoter. On the contrary, repression of the collagenase gene, does not require binding of the GR to an HRE, and involves an interaction of the receptor with the components of the AP1 complex, jun and fos. This inhibitory effect is reciprocal, in that fos and jun block glucocorticoid induction of HRE containing genes.