Androgen regulation of the Pem homeodomain gene in mice and rat Sertoli and epididymal cells.

Although the role of homeodomain transcription factors during embryogenesis is well known, their developmental function in postnatal animals is only beginning to be understood. We examined the regulation and expression pattern of Pem, a homeodomain protein that may regulate androgen-dependent events in the testis and epididymis. Immunohistochemical analysis showed that Pem protein is expressed selectively in the nuclei of Sertoli cells during the androgen-dependent stage of the seminiferous epithelium cycle in vivo. RNase protection analysis revealed that a proximal promoter was responsible for androgen-dependent mouse Pem expression in testis and epididymis in vivo, whereas a distal promoter was used in placenta. The mouse Pem gene was expressed at approximately 10-fold higher levels in the testis than in the epididymis; conversely, the rat Pem gene was expressed at >10-fold higher levels in the epididymis than in the testis. Because androgen-binding protein has been proposed to transport androgens from the testis to the epididymis, we tested whether the > or = 20-fold higher levels of androgen-binding protein expression in the rat, compared to that of mouse, are responsible for the differential expression of Pem in these two rodent species. Studies with androgen-binding protein transgenic mice demonstrated that the species-specific difference in androgen-binding protein expression is unlikely to be responsible for the species-specific difference in Pem expression. We found that androgen is necessary but not sufficient for Pem expression, since purified Sertoli cells rapidly down-regulated Pem transcripts in culture, regardless of the presence of testosterone. We conclude that Pem gene expression in Sertoli cells requires other cell types or cellular factors in addition to androgen.