title: Expression and localization of androgen receptor-interacting protein-4 in the testis.
abstract: Androgen receptor-interacting protein 4 (ARIP4) belongs to the SNF2 family of proteins involved in chromatin remodeling, DNA excision repair, and homologous recombination. It is a DNA-dependent ATPase, binds to DNA and mononucleosomes, and interacts with androgen receptor (AR) and modulates AR-dependent transactivation. We have examined in this study the expression and cellular localization of ARIP4 during postnatal development of mouse testis. ARIP4 was detected by immunohistochemistry in Sertoli cell nuclei at all ages studied, starting on day 5, and exhibited the highest expression level in adult mice. At the onset of spermatogenesis, ARIP4 expression became evident in spermatogonia, pachytene, and diplotene spermatocytes. Immunoreactive ARIP4 antigen was present in Leydig cell nuclei. In Sertoli cells ARIP4 was expressed in a stage-dependent manner, with high expression levels at stages II-VI and VII-VIII. ARIP4 expression patterns did not differ significantly in testes of wild-type, follicle-stimulating hormone receptor knockout, and luteinizing hormone receptor knockout mice. In testes of hypogonadal mice, ARIP4 was found mainly in interstitial cells and exhibited lower expression in Sertoli and germ cells. In vitro stimulation of rat seminiferous tubule segments with testosterone, FSH, or forskolin did not significantly change stage-specific levels of ARIP4 mRNA. Heterozygous ARIP4(+/-) mice were haploinsufficient and had reduced levels of Sertoli-cell specific androgen-regulated Rhox5 (also called Pem) mRNA. Collectively, ARIP4 is an AR coregulator in Sertoli cells in vivo, but the expression in the germ cells implies that it has also AR-independent functions in spermatogenesis.
authors.affiliation: Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, Finland.
authors.forename: Andrii
authors.initials: A
authors.lastname: Domanskyi
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Zhang
authors.forename: Mirja
authors.initials: M
authors.lastname: Nurmio
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004265:DNA Helicases; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics; D013737:Testis / Q000201:enzymology* / Q000254:growth & development; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D011944:Receptors, Androgen; D011962:Receptors, FSH; D011974:Receptors, LH; C498048:Rhox5 protein, mouse; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; C488190:Rad54l2 protein, mouse