Endocrine Abstracts

Introduction: Testicular morphology and immunohistochemistry have never been reported in genetically documented adult patients with 5α-reductase type 2 deficiency (5α-R2 deficiency).

Case report: We describe the testicular histopathology of a 17-year-old XY female with primary amenorrhea, failure of pubertal breast development, virilization, clitoromegaly, and bilateral cryptorchidism (testes located in the inguinal canals). The diagnosis of 5α-R2 deficiency was confirmed by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene. We performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case. We evaluated the testicular expression of the anti-Müllerian hormone (AMH), androgen receptor (AR), and 3β-hydroxysteroid dehydrogenase (3βHSD). Histological analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous tubules (ST) presenting a mature aspect but containing only Sertoli cells and devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were also found. Testicular AR and 3βHSD expression were detected in adult male control, 5α-R2 deficiency and CAIS subjects. However, AMH expression was heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise repressed) in the 5α-R2 deficiency, conversely to normal adult testis in which AMH was uniformly repressed and to an adult CAIS testis in which AMH was uniformly and strongly expressed.

Conclusion: Intratesticular testosterone can repress AMH by itself, independently of its metabolism into dihydrotestosterone. We also confronted our results to the few post pubertal cases of 5α-R2 deficiency with available histological testicular description, reported in the literature and interpreted histological findings, in the more general context of evaluating the fertility potential of these patients if they were raised as males and were azoospermic.