Expression and Functional Role of Peroxisome Proliferator-Activated Receptor-(gamma) in Ovarian Folliculogenesis in the Sheep

Peroxisome proliferator-activated receptor (PPAR(gamma)) is a nuclear receptor that is activated by fatty acids and derivatives and the antidiabetic glitazones, which plays a role in the control of lipid and glucose homeostasis. In the present work, we tested the hypothesis that PPAR(gamma) plays a role in reproductive tissues by studying its expression and function in the hypothalamo-pituitary-ovary axis in the sheep. PPAR(gamma) 1 and PPAR(gamma) 2 proteins and mRNAs were detected in whole ovine pituitary and ovary but not in hypothalamic extracts. In situ hybridization on ovarian section localized PPAR(gamma) mRNA in the granulosa layer of follicles. Interestingly, PPAR(gamma) expression was higher in small antral (1–3 mm diameter) than in preovulatory follicles (>5 mm diameter) (P < 0.001) and was not correlated with healthy status. To assess the biological activity of ovarian PPAR(gamma), ovine granulosa cells were transfected with a reporter construct driven by PPAR(gamma)-responsive elements. Addition of rosiglitazone, a PPAR(gamma) ligand, stimulated reporter gene expression, showing that endogenous PPAR(gamma) is functional in ovine granulosa cells in vitro. Moreover, rosiglitazone inhibited granulosa cell proliferation (P < 0.05) and increased the secretion of progesterone in vitro (P < 0.05). This stimulation effect was stronger in granulosa cells from small than from large follicles. In contrast, rosiglitazone had no effect on LH, FSH, prolactin and growth hormone secretion by ovine pituitary cells in vitro. Overall, these data suggest that PPAR (gamma) ligands might stimulate follicular differentiation in vivo likely through a direct action on granulosa cells rather than by modulating pituitary hormone secretion.