Interactions between insulin, IGFBP-1, IGFBP-2, SHBG, IGF-I bioavailability, the insulin receptor-A, the IGF-I receptor, estradiol and the estradiol receptor. Inhibitory effects are shown in red and stimulatory effects in green. Insulin stimulates the insulin receptor A (directly) and increases bioavailable IGF-I and estradiol (indirectly). Note that there is also bidirectional cross-talk between the IGF-I receptor and the estradiol receptor. IGFBP-1 = insulin-like growth factor binding protein-1, IGFBP-2 = insulin-like growth factor binding protein-2, SHBG= sex hormone binding globulin, ↑ levels increase, ↓ levels decrease.