Transcription Repression by Steroid Hormone Receptors

The steroid hormone receptors can not only activate transcription, but can also repress transcription (review Beato, 1995). This function is mechanistically poorly understood. Repression by nuclear receptors has been observed for genes whose control regions have, apart from the HREs, binding sites for other transcription factors, e.g. AP-1 and NFxB. In AP-1 and NFxB controlled genes it has been observed that the steroid hormone receptors have an inhibitory effect on the transcription activation of both transcription factors. The mechanism of this mutual interaction remains unclear. 

The transcription factors AP-1 and NFkB are at the end of a signal cascade activated by growth factors (see chapters 9,10,11), The ability of steroid hormone receptors in certain situations to nullify the effect other transcription factors demonstrates that two different signaling pathways can converge at the level of transcription. 

The observation that steroid hormone receptors act as activators as well as repressors of gene activity suggests that receptors can assume an activating and a repressing conformation. In the latter state, the transcriptional activating domain of the receptors is masked. 

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