Differential effects of prepubertal rat Sertoli cell secreted proteins on somatic testicular and nontesticular cells.

There is little information on the mitogenic and immunoregulatory activities of proteins, secreted by prepubertal Sertoli cells during the stage of meiosis initiation and before creation of the blood-testis barrier. We have previously demonstrated dose-dependent and age-related stimulation of BALB/c 3T3 fibroblasts and quiescent rat prespermatogonia (Kancheva et al., 1990) as well as inhibition of natural killer cell activity of mice, guinea pigs and human lymphocytes (Nikolova et al., 1992) by Sertoli cell-conditioned medium derived from 12-day-old rats. In the current study, using splenic lymphocytes stimulated by PHA, LPS and Con A, we have shown a dose-dependent inhibition of T and B lymphocyte proliferation by prepubertal Sertoli cell-secreted proteins (pSCSP). These results suggest that by the time the blood-testis barrier had been formed, Sertoli cell in rat testis had already synthesized immunoregulatory proteins. In addition we have found that pSCSP stimulate the proliferation of TM3 Leydig but not TM4 Sertoli cells. The differential effect of pSCSP is an expression of the different balance between growth factors secreted by Sertoli cells, which in turn is dependent on the requirements of the cell types at each stage of testicular development.

Prepubertal rat Sertoli cells secrete a mitogenic factor(s) that stimulates germ and somatic cell proliferation.

Sertoli cells were isolated from prepubertal 6- and 12-day-old rats. The Sertoli cell-conditioned media (SCCM-6 and SCCM-12) can markedly stimulate the proliferation of somatic cells and quiescent rat prespermatogonia in a dose-dependent and an age-related manner. SCCM-12 stimulated cell proliferation of BALB/c 3T3 fibroblasts up to 7-fold over control values, but did not stimulate to the same degree the germ cell mitotic activity. SCCM-6 stimulated proliferation of prespermatogonia up to 5-10-fold over controls. The mitogenic factor(s) in SCCM-6 appears to be more specific to prespermatogonia than to somatic cells which is consistent with the in vivo stimulation of mitosis in germ cells 5-6 days after birth and with the action of 'mitosis inducing substance'. The mitogenic factor(s) appears to be protein with a molecular weight over 8000 and sensitive to heat and trypsin treatment. These results suggest that the different mitogenicity of prepubertal rat SCCM on germ and somatic cells may be due to secretion of multiple mitogens by Sertoli cells in an age-dependent manner.