Germ cell-Sertoli cell interactions. Studies of cyclic protein-2 in the seminiferous tubule

This review briefly describes the discovery and isolation of a novel Sertoli cell product, cyclic protein-2, (CP-2) and the generation of an antiserum against this protein. Using this antiserum, we demonstrated a stage-specific change in the synthesis of CP-2 by Sertoli cells within intact seminiferous tubules; synthesis is maximal at stages VI and VIIa,b of the cycle and minimal at stage XII. That CP-2 is a product of Sertoli cells was confirmed by immunohistochemical analysis. Comparison of CP-2 and transferrin synthesis by immature (17-day) and mature (75-day) Sertoli cells within intact seminiferous tubules has documented a significant increase in the synthesis of both proteins during testicular maturation. It was noteworthy, however, that the increase in CP-2 synthesis was much greater than the increase in transferrin synthesis. These data in conjunction with previous comparisons of the stage-specific changes in CP-2 and transferrin synthesis and secretion led to the hypothesis that the synthesis of these two proteins is regulated by different cellular interactions. Examination of cultured Sertoli cells obtained from mature rats demonstrated that transferrin synthesis and secretion were stimulated by hormones and vitamins, whereas CP-2 synthesis and secretion were not significantly affected by the same factors. Therefore, these data demonstrate that hormonal regulation of transferrin synthesis by Sertoli cells differs from hormonal regulation of CP-2 synthesis. Indeed, our data suggest that CP-2 synthesis is not directly regulated by hormones and vitamins. Finally, we demonstrated that when Sertoli cells are separated from germ cells and the Sertoli cells placed in culture, the age-dependent increase in CP-2 synthesis, noted with cultured tubules, is lost. In contrast, significantly more transferrin is synthesized by primary cultures of Sertoli cells obtained from old animals than from young animals. Taken together, all of these data indicate that the regulation of CP-2 synthesis and secretion by the Sertoli cell is unique and is primarily stimulated by paracrine signals or direct cell contact with the germ cells. Which of these mechanisms of cell-cell communication in the testis is important to regulation of CP-2 synthesis by Sertoli cells is unknown. Neither do we know which spermatogenic cell type provides this stimulus. These issues can now be addressed, however, because we have developed the protocols for isolating and culturing Sertoli cells from mature rat testes.