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Physiological Androgen Insensitivity of the Fetal, Neonatal, and Early Infantile Testis Is Explained by the Ontogeny of the Androgen Receptor Expression in Sertoli Cells

Centro de Investigaciones Endocrinológicas (Consejo Nacional de Investigaciones Cientificas y Técnicas) (H.E.C., R.A.R., M.M.), Hospital de Niños R. Gutiérrez, C1425EFD Buenos Aires, Argentina; Departamento de Histología, Biología Celular, Embriología, y Genética (R.A.R.), Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina; Departamento de Patología (M.N., J.R.), Hospital La Paz, 28046 Madrid, Spain; Departamento de Anatomía, Histología, y Neurociencia (M.N.), Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain; and Departamentos de Patología y Urología (P.G.-P., A.S.), Hospital Universitario de Guadalajara, Universidad de Alcalá, 19002 Guadalajara, Spain

Address all correspondence and requests for reprints to: Dr. Héctor Chemes, Centro de Investigaciones Endocrinológicas (CEDIE-Consejo Nacional de Investigaciones Científicas y Técnicas), Hospital de Niños R. Gutiérrez, C1425EFD Buenos Aires, Argentina. E-mail: hchemes{at}cedie.org.ar.

Context: Although gonadotropins and testosterone are high in the fetal/early postnatal periods, Sertoli cells remain immature and spermatogenesis does not progress. We hypothesized that Sertoli cells do not respond to testosterone because they do not express the androgen receptor.

Objective: The objective of the study was to describe the precise ontogeny of androgen receptor expression in the human testis from fetal life through adulthood.

Design: This was an immunohistochemical study on testicular biopsies from fetal, neonatal, prepubertal, pubertal, and adult human testes.

Main Outcome Measures: Quantification of androgen receptor expression in Sertoli cells was measured. Evaluation of androgen receptor expression in peritubular and interstitial cells as well as anti-Müllerian hormone and inhibin- was also performed.

Results: Androgen receptor expression was first observed in the nuclei of few Sertoli cells at the age of 5 months. Labeling was weak in 2–15% of Sertoli cells until 4 yr of age and progressively increased thereafter. High levels of androgen receptor expression were observed in more than 90% from the age of 8 yr through adulthood. Androgen receptor was positive in peritubular cells and variable in interstitial cells. Anti-Müllerian hormone immunolabeling was strong in all Sertoli cells from fetal life throughout prepuberty and weakened progressively as spermatogenesis developed. Inhibin- expression was detected in all Sertoli cells from fetal life through adulthood.

Conclusions: A lack of androgen receptor expression could explain a physiological Sertoli cell androgen insensitivity during fetal and early postnatal life, which may serve to protect the testis from precocious Sertoli cell maturation, resulting in proliferation arrest and spermatogenic development.

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