While in the ovary of PCOS patients insulin most likely acts as a co-gonadotropin, enhancing the stimulating effects of LH on androgen synthesis in theca cells [46,47], increased insulin receptor signaling in adrenals should be considered for a better understanding of the controversial mechanisms of adrenal hyperandrogenism of PCOS [45], a complex genetic disease characterized by specific reproductive and metabolic abnormalities including elevated androgen levels and hyperinsulinemia which are present not only in PCOS subjects but also in their male and female relatives [1]. This evidence concerns the gene INSR and hyperinsulinism.