THE ANDROGEN-SPECIFIC PROBASIN RESPONSE ELEMENT-2 INTERACTS DIFFERENTIALLY WITH ANDROGEN AND GLUCOCORTICOID RECEPTORS

The nuclear receptors constitute a large family of transcription facto rs characterized by a well conserved DNA-binding domain. The receptors for glucocorticoids, progestins, mineralocorticoids, and androgens co nstitute a subgroup because they bind in vitro with high affinity to D NA elements containing a partial palindrome of the core sequence 5'-TG TTCT-3'. In vivo, however, the corresponding steroids differentially r egulate the expression of their target genes, even when more than one receptor type is present in a particular cell. The DNA-binding domains of the androgen and of the glucocorticoid receptors bind most androge n response elements with similar relative affinities. In contrast, one element (5'-GGTTCTTGGAGTACT-3') which was recently described in the p romoter region of the probasin gene selectively interacts with the DNA -binding domain of the androgen receptor and not with that of the gluc ocorticoid receptor. From studies with chimeric elements, it can be de duced that it is the left subsequence 5'-GGTTCT-3' which excludes the glucocorticoid receptor domain from binding. In co-transfection experi ments where the ARE of the C3(1) gene is responsive to both androgens and glucocorticoids, the probasin element is induced only by androgens and not by glucocorticoids. The existence of response elements which are recognized preferentially by the androgen receptor provides yet an other possible mechanism to explain the differences of the in vivo eff ects between androgens and other steroids of the subgroup.