Hyperinsulinemia synergizes with LH on theca cells, upregulating CYP17A1 transcription and cytochrome P450 17α-hydroxylase (P450c17α) activity while simultaneously lowering hepatic sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein-1 (IGFBP-1) [11,20,21,22,23,24,25,26]. The gene discussed is IGFBP1; the disease is hyperinsulinism.