Molecular insights into hormone regulation via signaling pathways in Sertoli cells: With discussion on infertility and testicular tumor

Spermatogenesis is a complex and elaborate differentiation process and is critical for male fertility. The hypothalamic-pituitary-gonadal axis serves as a significant neuroendocrine system to regulate spermatogenesis. As a constitute of the hypothalamic-pituitary-gonadal axis, Sertoli cells promote spermatogenesis via protecting, nourishing, and supporting germ cells upon hormone determination. Here we clarified how the hormones in the hypothalamic-pituitary-gonadal axis, including FSH, testosterone and LH, regulate spermatogenesis via the androgen receptor, cAMP/PKA, PI3k/Akt signaling pathways in Sertoli cells. Other endogenous hormones in higher vertebrates, including ouabain, estradiol, leptin, MIS, PGD(2), and thyroid hormone, also regulate spermatogenesis via the AR or cAMP/PKA signaling pathway. Among them, the dynamics of adherens junctions, gap junctions, and blood-testis barrier, glucose uptake, lactate supply and differentiation of Sertoli cells are regulated by more comprehensive hormones and signaling pathways in Sertoli cells. In infertile patients or patients with blocked spermatogenesis, the AR, cAMP/PKA and PI3k/Akt signaling pathways and related components exhibit abnormal activity or disordered content. The clinical specimens from patients with testicular cancer show similar mutated AR genes. According to the existing clinical evidence, it is valuable to study the deep mechanism of male infertility and testicular tumors from the perspective of hormones and signaling pathways in Sertoli cells.