SOMATOMEDIN-C (Sm-C/IGF-1) SYNERGISES WITH FIBROBLAST GROWTH FACTOR (FGF) ON SERTOLI CELLS (SC) MULTIPLICATION AND DIFFERENTIATION

Abstract

We have characterized Sm-C secretion and regulation by immature porcine SC cultured (ESPE 86). The present study evaluates the autocrine action of Sm-C on SC. The presence of IGF type I receptors on SC was identified by binding (Kd = 10−9 M) and cross-linking. No detectable insulin receptor was found. FGF and Sm-C stimulate SC DNA synthesis with observed ED50 of 2.0 and 7.5 ng/ml respectively. Synergistic effect of FGF+Sm-C was found at saturating concentration of both factors. SC multiplication was increased compared to controls by Sm-C, FGF, Sm-C + FGF by a factor of 1.65, 2.05 and 3.2 respectively. When SC function was studied, FSH receptor number was increased by 1.65, 2.05 and 3.2 respectively. When SC function was studied, FSH receptor number was increased by 1.6 by FGF alone with no effect per se nor synergistic of Sm-C. FSH stimulated cAMP secretion by SC was enhanced by FGF (140%), FGF+Sm-C (195%), but not Sm-C alone. When Plasminogen Activator-secretion by SC was measured, a 3.0 and 22 time increase in basal secretion was observed with FGF and FGF+Insulin respectively compared with controls; furthermore, in the presence of FGF and FGF+Insulin, additional 3.3 and 1.24 respective increment factors were observed after FSH stimulation. All the insulin effects were observed at 5 μg/ml and are likely to be mediated through IGF type 1 receptors. Conclusions: These data demonstrate that Sm-C/IGF-1 secreted by SC may have an autocrine effect expressed by the stimulation of SC multiplication and by the synergistic effect with FGF on SC function. These effects of Sm-C on SC, combined to its paracrine effects on Leydig cells (ESPE 86) emphasize the complex but key actions of Sm-C on testicular function and its maturation.