title: Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients.
abstract: Androgen receptor (AR) is essential for testicular physiology and spermatogenesis. SRC-2 and HBO1 are two AR coregulators yet their expression and roles in human testis are unknown. For the first time, we studied by immunohistochemistry and RT-PCR, the expression and distribution of these two coregulators during human testicular ontogenesis, in patients with altered AR signaling (Androgen insensitivity syndrome, AIS) and evaluated the functional impact of SRC-2 and HBO1 on AR signaling in a Sertoli cell context. SRC-2 was present in Sertoli cells at all developmental stages. HBO1 was barely or focally detected in the fetal testis yet its expression, in Sertoli and germ cells, drastically increased postnatally from early infancy to adulthood. In transient co-transfection studies we showed that SRC-2 induced, while HBO1 inhibited AR-mediated transactivation of reporter constructs in murine Sertoli SMAT1 cells. HBO1, but not SRC-2, expression was reduced in testes of patients with AIS compared to normal testes.
authors.affiliation: Univ Paris-Sud, Faculté de Médecine Paris-Sud, UMR-S693, Le Kremlin-Bicêtre F-94276, France.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Vija
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.forename: Eva
authors.initials: E
authors.lastname: Comperat
authors.forename: Viorel
authors.initials: V
authors.lastname: Vasiliu
authors.forename: Vincent
authors.initials: V
authors.lastname: Izard
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Kahina
authors.initials: K
authors.lastname: Boukari
authors.forename: Philippe
authors.initials: P
authors.lastname: Camparo
authors.forename: Say
authors.initials: S
authors.lastname: Viengchareun
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Constancis
authors.forename: Constantin
authors.initials: C
authors.lastname: Dumitrache
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D013196:Dihydrotestosterone / Q000494:pharmacology; D004790:Enzyme Induction; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011944:Receptors, Androgen / Q000378:metabolism; D012671:Seminiferous Tubules / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013091:Spermatogenesis; D055815:Young Adult
chemical_list: D000728:Androgens; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human