title: Lack of androgen receptor expression in Sertoli cells accounts for the absence of anti-Mullerian hormone repression during early human testis development.
abstract: BACKGROUND
  Puberty is associated with increased testicular testosterone (TT) synthesis, which is required to trigger spermatogenesis and to repress anti-Mullerian hormone (AMH) production. However, testicular gonadotropin stimulation during fetal and newborn life neither initiates spermatogenesis nor represses AMH.
  
  
  OBJECTIVE
  We postulated that a lack of androgen receptor (AR) expression in Sertoli cells (SC) might explain why these processes do not occur during early human development.
  
  
  METHODS
  Using immunohistochemistry and quantitative PCR, we examined the relationship between AR, AMH, and FSH receptor expression in fetal, newborn, and adult human testis. The ability of testosterone to repress AMH secretion was evaluated in male newborns, neonates, and two adults with androgen insensitivity syndrome and also in vitro using SMAT1 SC.
  
  
  RESULTS
  FSH receptor was present in SC at all developmental stages. In fetal and newborn testis, AR was expressed in peritubular and Leydig cells but not in SC. This coincided with the absence of spermatogenesis and with strong SC AMH expression. In adult testis, spermatogenesis was associated with AR expression and with a decrease in SC AMH content. Accordingly, AR mRNA expression was lower and AMH mRNA expression higher in fetal testes than in adult testes. In androgen insensitivity syndrome patients, combined gonadotropin stimulation induced an increase in circulating testosterone and AMH, a finding consistent with a failure of TT to repress AMH in the absence of AR signalling. Finally, direct androgen repression of AMH only occurred in AR-expressing SMAT1 cells.
  
  
  CONCLUSIONS
  Functional ARs are essential for TT-mediated AMH repression in SC.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unit 693, F-94276 Le Kremlin Bicêtre, France.
authors.forename: Kahina
authors.initials: K
authors.lastname: Boukari
authors.forename: Geri
authors.initials: G
authors.lastname: Meduri
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.forename: Jean
authors.initials: J
authors.lastname: Guibourdenche
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Ciampi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Massin
authors.forename: Laetitia
authors.initials: L
authors.lastname: Martinerie
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Picard
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Rey
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000378:metabolism; D054304:Anti-Mullerian Hormone / Q000096:biosynthesis*; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007231:Infant, Newborn; D008297:Male; D016612:Paraffin Embedding; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis*; D011962:Receptors, FSH / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D011962:Receptors, FSH; D054304:Anti-Mullerian Hormone; D015096:3-Hydroxysteroid Dehydrogenases