The adiponectin agonist, AdipoRon, inhibits steroidogenesis and cell proliferation in human luteinized granulosa cells

• Published in: Molecular and cellular endocrinology Vol. 520; p. 111080
• Main Authors: Grandhaye, Jérémy, Hmadeh, Sandy, Plotton, Ingrid, Levasseur, Floriane, Estienne, Anthony, LeGuevel, Rémy, Levern, Yves, Ramé, Christelle, Jeanpierre, Eric, Guerif, Fabrice, Dupont, Joëlle, Froment, Pascal
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.01.2021; Elsevier
• Subjects: Adiponectin; Adiporon; Endocrinology and metabolism; Human health and pathology; Human luteinized granulosa cells; Life Sciences; Steroid; Steroid; Adiporon; Human luteinized granulosa cells; Adiponectin
• ISSN: 0303-7207; 1872-8057; 0303-7207
• DOI: 10.1016/j.mce.2020.111080

During obesity, excess body weight is not only associated with an increased risk of type 2-diabetes, but also several other pathological processes, such as infertility. Adipose tissue is the largest endocrine organ of the body that produces adipokines, including adiponectin. Adiponectin has been reported to control fertility through the hypothalamic–pituitary–gonadal axis, and folliculogenesis in the ovaries. In this study, we focused on a recent adiponectin-like synthetic agonist called AdipoRon, and its action in human luteinized granulosa cells. We demonstrated that AdipoRon activated the adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR) signalling pathways in human luteinized granulosa cells. A 25 μM AdipoRon stimulation reduced granulosa cell proliferation by inducing cell cycle arrest in G1, associated with PTEN and p53 pathway activation. In addition, AdipoRon perturbed cell metabolism by decreasing mitochondrial activity and ATP production. In human luteinized granulosa cells, AdipoRon increased phosphodiesterase activity, leading to a drop in cyclic adenosine monophosphate (cAMP) production, aromatase expression and oestrogens secretion. In conclusion, AdipoRon impacted folliculogenesis by altering human luteinized granulosa cell function, via steroid production and cell proliferation. This agonist may have applications for improving ovarian function in metabolic disorders or granulosa cancers. •AdipoRon an Adiponectin agonist which could be an interesting drug in the treatment of infertile women with PCOS.•However, none or little information are available about the action of AdipoRon in granulosa cells, which nursed the oocyte.•In this study, we investigated the role of AdipoRon on viability, cell proliferation, and steroidogenesis.