However, in vivo and in vitro studies confirmed that insulin excess stimulates further androgen production in ovaries via insulin receptors on theca/interstitial ovarian stromal cells, therefore aggravating already increased ovarian androgen production in PCOS and lowering the hepatic sex-hormone binding globulin (Smith et al., 1987; Plymate et al., 1988; Nestler et al., 1998; Baillargeon, 2007; Rosenfield and Ehrmann, 2016). This evidence concerns the gene INS and polycystic ovary syndrome.