Noticeably, IR in PCOS does not involve ovarian tissue, leading to an increase in its gonadotropic effect: insulin acts as a co-gonadotropin through an indirect mechanism, enhancing luteinizing hormone (LH) action on theca cells, and through a direct mechanism that induces higher hypothalamic secretion of LH, leading to increased dehydroepiandrosterone (DHEA) and androstenedione production [26]. This evidence concerns the gene PLOD1 and polycystic ovary syndrome.