Promoter specific regulation

The transcriptional activation method with different androgen-dependent promoters may be implemented to find dissociated androgens. The structure of promoters of AR target genes were described including one or more binding sites for the receptor. Subtle differences in the sequence of response elements can dictate androgen specific responses and creates new possibilities in the research on hormone-selective action and provides a new angle in the search for selective lig-ands that might influence AR mediated action via the type of DNA motif (Verrijdt etal. 2003). The rat probasin promoter, the human secretory component upstream enhancer and the mouse sex-limited protein enhancer are examples of elements specifically regulated by androgens involving androgen-specific DNA regions. As ligand bound AR interacts with the DNA, the conformation of the receptor will be altered. This was shown for the ER interaction with the DNA (see 20.2.3), but no data are available for AR. However, it is very likely that also for the AR individual AREs cause distinct conformation changes of the receptor. Particular ligands may alter the AR conformation synergistically with the individual ARE. Use and comparison of distinct androgen-dependent gene promoters might be a rationale for the identification of androgens with selective action.

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