Physiological androgen insensitivity of the fetal, neonatal, and early infantile testis is explained by the ontogeny of the androgen receptor expression in Sertoli cells.
BACKGROUND
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.


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


METHODS
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-alpha 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-alpha 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.
Chemes
Héctor E
HE
Centro de Investigaciones Endocrinológicas, Hospital de Niños R. Gutiérrez, and Departamento de Histología, Biología Celular, Embriología, y Genética, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. hchemes@cedie.org.ar
Rey
Rodolfo A
RA
Nistal
Manuel
M
Regadera
Javier
J
Musse
Mariana
M
González-Peramato
Pilar
P
Serrano
Alvaro
A
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000502:physiology*; D054304:Anti-Mullerian Hormone / Q000502:physiology; D002455:Cell Division; D002467:Cell Nucleus / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics*; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology*; D013091:Spermatogenesis; D013737:Testis / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development / Q000502:physiology*; D055815:Young Adult
D000728:Androgens; D011944:Receptors, Androgen; D054304:Anti-Mullerian Hormone