The involvement of insulin-like growth factor-I in local control of steroidogenesis and DNA synthesis of Leydig and non-Leydig cells in the rat testicular interstitium
ABSTRACT Insulin-like growth factor-I (IGF-I) peptide, receptors and binding proteins are present in the rodent testis, which strongly implies that IGF-I has one or more testicular functions. In the present study we provide further information to support the concept that IGF-I is an important local mediator in the testis. High concentrations of IGF-I were measurable in interstitial fluid by radioimmunoassay, and IGF-I-binding proteins (IGFBPs) were readily detectable in interstitial fluid by ligand blotting, the predominant type being IGFBP-2. In vitro, IGF-I bound to testicular interstitial cells which did not have 3β-hydroxysteroid dehydrogenase (3β-HSD) activity and which were resistant to ethane dimethanesulphonate treatment. In vitro, IGF-I receptor-mediated actions increased both steroidogenesis and DNA synthesis. Insulin stimulated DNA synthesis at concentrations appropriate to cross-react with the IGF-I receptor, and this effect was greater in a testicular interstitial Leydig cell-depleted cell population compared with a Leydig cell-enriched cell culture. Furthermore, combinations of epidermal growth factor or transforming growth factor -α together with insulin appeared to act synergistically, causing extremely large increases in [3 H]thymidine incorporation in the interstitial cells. These results support a paracrine and/or autocrine role for IGF-I in interstitial cell growth and development. Journal of Endocrinology (1993) 138, 107–114