In line with this speculation, we have proved that the expression of the NPPC/NPR2 system in ovarian granulosa cells is up regulated by sex hormones, such as androgen and estrogen through respective hormone receptors (AR and ER) in physiological conditions, in polycystic ovary syndrome (PCOS) in mice ovaries, and in in vitro cultured granulosa cell lines (Liu et al., 2017; Reis and Honorato-Sampaio, 2018; Wang et al., 2018). This evidence concerns the gene NR4A1 and polycystic ovary syndrome.