Hyperinsulinemia decreases the hepatic synthesis of SHBG and this mechanism contributes to the increase of the free androgens and consequently the peripheral androgen action; moreover, hyperinsulinemia also blocks the hepatic secretion of the IGF binding protein- (IGFBP-) 1, resulting in an increased bioactivity of IGF-I and IGF-II which are two important regulators of ovarian follicular maturation and steroidogenesis [30]. The gene discussed is SHBG; the disease is hyperinsulinism.