Figure 3.

The classical and non-classical pathways of androgen between the two neighboring Sertoli cells allow the germ cells to continuously mature and move toward the lumen. The classic androgen pathway is shown in the Sertoli cells on the left. Androgen diffuses into the cytoplasm through the plasma membrane and interacts with HSP-binding AR, then the AR dissociates from HSP and localizes to the nucleus. In the nucleus, AR homodimers recruit co-regulators and bind to the ARE of the target gene to regulate their transcription. The classic pathways guarantee Sertoli cell maturation, BTB integrity, SSC differentiation, and spermatocyte meiosis. The non-classical androgen pathway is depicted within the Sertoli cells on the right. Androgen binds to AR on the cell membrane and subsequently interacts with Src. Src then activates EGFR, initiating a series of cascade reactions. Ultimately, the phosphorylated p90Rsk translocates to the nucleus and activates CREB to bind to the CRE of the target genes, thereby regulating their transcription. This process enables androgens to modulate the BTB integrity of Sertoli cells, the meiosis of spermatocytes, Sertoli cell–spermatid adhesion, spermatid development, and sperm release.