ANDROGEN REGULATION OF THE PEM HOMEODOMAIN GENE IN MICE AND RAT SERTOLI AND EPIDIDYMAL CELLS

Although the role of homeodomain transcription factors during embryoge nesis is well known, their developmental function in postnatal animals is only beginning to be understood. We examined the regulation and ex pression pattern of Pem, a homeodomain protein that may regulate andro gen-dependent events in the testis and epididymis. Immunohistochemical analysis showed that Pem protein is expressed selectively in the nucl ei of Sertoli cells during the androgen-dependent stage of the seminif erous epithelium cycle in vivo. RNase protection analysis revealed tha t a proximal promoter was responsible for androgen-dependent mouse Pem expression in testis and epididymis in vivo, whereas a distal promote r was used in placenta. The mouse Pem gene was expressed at approximat e to 10-fold higher levels in the testis than in the epididymis; conve rsely, the rat Pem gene was expressed at >10-fold higher levels in the epididymis than in the testis. Because androgen-binding protein has b een proposed to transport androgens from the testis to the epididymis, we tested whether the greater than or equal to 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 thes e two rodent species. Studies with androgen-binding protein transgenic mice demonstrated that the species-specific difference in androgen-bi nding protein expression is unlikely to be responsible for the species -specific difference in Pem expression. We found that androgen is nece ssary but not sufficient for Pem expression, since purified Sertoli ce lls rapidly down-regulated Pem transcripts in culture, regardless of t he presence of testosterone. We conclude that Pem gene expression in S ertoli cells requires other cell types or cellular factors in addition to androgen.