Peroxisome proliferator-activated receptors (PPARs) and ovarian function – implications for regulating steroidogenesis, differentiation, and tissue remodeling

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors belonging to the steroid receptor superfamily. Issemann and Green identified the first PPAR in 1990 [1], and subsequently, two other family members were discovered. To date, PPARs have been identified in a variety of species from chickens [2] and fish [3], to humans (reviewed in [4,5]).Although a great deal has been learned about PPARs since their discovery, very little is known regarding how these factors impact ovarian function. This review describes the expression of the PPARs in the ovary, and highlights the roles of these transcription factors that may affect ovarian biology. The influence of PPARs on polycystic ovary syndrome (PCOS) is not discussed in this review. There is a large body of literature on the use of thiazolidinediones, a class of drugs that activate PPARγ, in the treatment of women with PCOS. However, because these drugs can have direct effects on the ovary independent of activating PPARγ [6], and indirectly influence ovarian biology by lowering insulin levels, it is hard to discern PPARγ-dependent versus -independent effects. Therefore, this review focuses on the potential of PPARs to impact normal ovarian function and the development of ovarian tumors.There are three PPAR family members: PPARα (NR1C1), PPARδ [NUC-1, fatty acid-activated receptor (FAAR), β, NR1C2], and PPARγ (NR1C3). The PPARs share a common structure with other steroid hormone receptors (Figure 1A). The N-terminal A/B domain is responsible for ligand-independent transactivation function (AF-1); the C domain contains the DNA-binding domain; the D domain – also called the hinge region, plays a role in receptor dimerization; and the C-terminal E/F domain contains the ligand binding domain (AF-2).Each PPAR family member is transcribed from a specific gene. Alternative splicing and the use of different promoters give rise to different splice variants of each PPAR family member (Figure 1B).