This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Boukari, K. Articles by Young, J. Search for Related Content PubMed PubMed Citation Articles by Boukari, K. Articles by Young, J. Related Collections Male Endocrinology

Lack of Androgen Receptor Expression in Sertoli Cells Accounts for the Absence of Anti-Mullerian Hormone Repression during Early Human Testis Development

Institut National de la Santé et de la Recherche Médicale Unit 693 (K.B., G.M., S.B.-T., L.M., M.L., J.Y.), F-94276 Le Kremlin Bicêtre, France; Université of Paris-Sud 11 (K.B., S.B.-T., L.M., M.L., J.Y.), Faculté de Médecine Paris-Sud, Unité Mixte de Recherche-S693, F-94276 Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris (G.M., S.B.-T.), Hôpital de Bicêtre, Service de Génétique Moléculaire, Pharmacogénétique, et Hormonologie, F-94275 Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris (J.G.), Hôpital Robert Debré, Service de Biochimie, 75019 Paris, France; Department of Pathology (M.L.C.), University of Bari, 70121 Bari, Italy; Centre d’Assistance Médicale à la Procréation (N.M.), Université Paris 12, Centre Hospitalier Intercommunal, F-94010 Créteil Cedex, France; INSERM U782 (J.-Y.P.), F-92140 Clamart, France; Centro de Investigaciones Endocrinológicas (R.R.), Hospital de Niños R. Gutiérrez, 1330 Buenos Aires, Argentina; Assistance Publique-Hôpitaux de Paris (M.L., J.Y.), Hôpital de Bicêtre, Service d’Endocrinologie et Maladies de la Reproduction, F-94275 Le Kremlin Bicêtre, France

Address all correspondence and requests for reprints to: Jacques Young, M.D., Ph.D., Institut National de la Santé et de la Recherche Médicale Unit 693, Faculté de Médecine Paris-Sud, 63, rue Gabriel Péri, F-94276 Le Kremlin Bicêtre, France. E-mail: jacques.young{at}bct.aphp.fr.

Context: 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 and Patients: 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.

Conclusion: Functional ARs are essential for TT-mediated AMH repression in SC.