Rosiglitazone stimulates peroxisome proliferator-activated receptor gamma expression and directly affects in vitro steroidogenesis in porcine ovarian follicles

Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) synthetic activator from the group of thiazolidinediones often used in the treatment of chronic diseases such as type 2 diabetes and other forms of insulin resistance. The present in vitro study assessed the direct effects of rosiglitazone at 25 and 50 μM doses on PPARγ gene expression, steroid secretion (progesterone P4], androstenedione A4], testosterone T], and estradiol), and protein expression of PPARγ, 3βHSD, CYP17, 17βHSD, CYP19 by porcine ovarian follicles from prepubertal and cycling animals. We analyzed also steroid enzymatic activity by conversion of pregnen-3β-ol-20-one to P4, P4 to A4, and A4 to T. Our results indicated that rosiglitazone increased significantly PPARγ expression, P4 secretion, 3βHSD activity, and protein expression. Rosiglitazone decreased A4 and T secretion by reducing the expression and activity of CYP17 and 17βHSD and did not change estradiol secretion and CYP19. Similarly results was observed both in prepubertal and cycling pigs. Our results indicate that these direct effects of rosiglitazone on ovarian steroidogenesis provide a framework for testing several potential new mechanisms of PPAR-γ actions on porcine ovarian function.