Direct Thiazolidinedione Action in the Human Ovary: Insulin-Independent and Insulin-Sensitizing Effects on Steroidogenesis and Insulin-Like Growth Factor Binding Protein-1 Production

• DOI: 10.1210/jc.2005-0469
• Publication Date: 2005-11-08T00:27:48Z
• Authors: Donna Seto-Young; Maria Paliou; Jonathan Schlosser; Dimiter Avtanski; Alice Park; Parini Patel; Kevin Holcomb; Peter Chang; Leonid Poretsky
• Keywords: Rosiglitazone; Pioglitazone; Thiazolidinedione; Hyperinsulinemia

Context and Objective: Hyperinsulinemia contributes to the pathogenesis of ovarian dysfunction in insulin-resistant states, including polycystic ovary syndrome (PCOS). Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists [thiazolidinediones (TZDs)] ameliorate hyperandrogenism presumably because they reduce systemic hyperinsulinemia. Direct effects TZDs ovary, however, cannot be excluded. We explored direct cultured human cells. Methods: Human cells, obtained from oophorectomy specimens, were presence or absence rosiglitazone pioglitazone, insulin, gonadotropins. Steroid hormone IGF-binding protein-1 (IGFBP-1) concentrations measured conditioned tissue culture medium. Results: Rosiglitazone pioglitazone stimulated progesterone production up 156% (P < 0.001) 131% baseline, respectively. Pioglitazone but not rosiglitazone, inhibited baseline FSH-stimulated estradiol by 20% 50% 0.001), Both abolished insulin-dependent stimulation FSH. testosterone 10% 0.012) 15% 0.023), respectively, insulin-induced production. In IGFBP-1 160% 125% 0.036) enhanced inhibition 13% 20%, respectively 0.001). Conclusions: PPAR-γ directly stimulate production, inhibit abolish FSH, enhance represents a novel system regulation.