Effect of androgens on Sertoli cell maturation in human testis from birth to puberty

BACKGROUND: Androgens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty. RESULTS: Testicular tissue samples were studied in a population of 84 control boys classified into seven groups according to age: group 1 (1–30 days), group 2 (1–3 months), group 3 (3–6 months), group 4 (0.5–3 years), group 5 (3–6 years), group 6 (6–12 years), and group 7 (12–16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12–16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age. CONCLUSIONS: Androgen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.