Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Figure 2

Insulin signaling in ovarian thecal cells and proposed mechanisms for selective insulin resistance. Solid lines represent well-characterized mechanisms. Dashed lines represent incomplete information or hypothetical mechanisms. (A) Insulin may act in synergy with LH to increase intracellular concentration of cAMP, potentiating PKA activation and subsequent phosphorylation of StAR, favoring steroidogenesis. (B) A hypothetical serine-kinase could unify hyperinsulinemia-hyperandrogenemia in PCOS, as it would inhibit Akt activity, negating the metabolic effects of insulin, while activating steroidogenic enzymes. Furthermore, the mitogenic pathway would be left intact and fully functional, favoring thecal proliferation. (C) Inositolphosphoglycan generation appears to be triggered by INSR-prompted mechanisms independent of signaling molecules within metabolic or mitogenic pathways on insulin signaling. Therefore, inositolphosphoglycans may stimulate steroidogenic activity regardless of metabolic and signaling disturbances typical of systemic insulin resistance.