PEM - A TESTOSTERONE-REGULATED AND LH-REGULATED HOMEOBOX GENE EXPRESSED IN MOUSE SERTOLI CELLS AND EPIDIDYMIS

Few transcription factors in somatic cells of the testis and epididymi s that could potentially regulate androgen-dependent developmental eve nts during male gametogenesis have been identified. In this study we e xamined the regulation and expression of an orphan homeobox gene, Pem, which encodes a homeodomain related to those in the Prd/Pax gene fami ly. RNase protection, in situ hybridization, and Northern blot analyse s of wild-type and germ-cell-deficient mutant mice (W-v/W-v) localized Pem transcripts to Sertoli cells of the testis. During prepubertal te sticular development, Pem expression was dramatically induced on Day 9 , approximately when germ cells are known to enter meiotic prophase. I n adult mice, Pem transcripts were preferentially expressed in stages VII-VIII seminiferous epithelium, the androgen-dependent stages during which germ cells undergo the first step of meiosis. Pem gene expressi on depended on androgens and gonadotrophins, as demonstrated by a lack of expression in hypophysectomized mice, gonadotrophin-deficient hypo gonadal(hpg) mutant mice, and androgen receptor-deficient (tfm) mutant mice. Injection of either testosterone or luteinizing hormone (LH) in to hypophysectomized and hpg/hpg mice restored Pem expression in the t estes to normal levels. The Pem gene was also shown to be specifically expressed in the proximal cauda and distal corpus regions of the epid idymis, the regions where spermatozoa gain forward motility and fertil ization competence. Pcm expression ill the epididymis did not depend o n spermatozoa in the lumen of the testis, as shown in quaking (qk/qk) mutant mice, however, unlike in the testes, epididymal Pem expression required germ-cell-induced factors. Our results show that discrete cel l types in male reproductive tissues transcribe and independently regu late the Pem homeobox gene. To our knowledge no transcription factors have previously been shown to depend on testosterone or LH for express ion in Sertoli cells in vivo. Collectively, the data implicate Pem as a candidate to regulate a subset of androgen-dependent genes in the ma le reproductive system. (C) 1996 Academic Press, Inc.