Pem: a testosterone- and LH-regulated homeobox gene expressed in mouse Sertoli cells and epididymis

Abstract

Few transcription factors in somatic cells of the testis and epididymis that could potentially regulate androgen-dependent developmental events during male gametogenesis have been identified. In this study we examined the regulation and expression of an orphan homeobox gene, Pem, which encodes a homeodomain related to those in the Prd/Pax gene family. RNase protection, in situ hybridization, and Northern blot analyses of wild-type and germ-cell-deficient mutant mice (W(V)/ W(V)) localized Pem transcripts to Sertoli cells of the testis. During prepubertal testicular development, Pem expression was dramatically induced on Day 9, approximately when germ cells are known to enter meiotic prophase. In 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 expression depended on androgens and gonadotrophins, as demonstrated by a lack of expression in hypophysectomized mice, gonadotrophin-deficient hypogonadal (hpg) mutant mice, and androgen receptor-deficient (tfm) mutant mice. Injection of either testosterone or luteinizing hormone (LH) into hypophysectomized and hpg/hpg mice restored Pem expression in the testes to normal levels. The Pem gene was also shown to be specifically expressed in the proximal cauda and distal corpus regions of the epididymis, the regions where spermatozoa gain forward motility and fertilization competence. Pem expression in the epididymis did not depend on 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 cell types in male reproductive tissues transcribe and independently regulate the Pem homeobox gene. To our knowledge no transcription factors have previously been shown to depend on testosterone or LH for expression in Sertoli cells in vivo. Collectively, the data implicate Pem as a candidate to regulate a subset of androgen-dependent genes in the male reproductive system.