Possible role of PPARγ in the negative regulation of ovulatory cascade and luteal development in rats

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ), a member of a nuclear receptor family, has been shown to be implicated in various reproductive processes. Here, we evaluated possible roles of PPARγ in ovulation and luteal development in a gonadotropins-primed immature rat model. Immunoreactive PPARγ was expressed in granulosa cells of eCG-stimulated mature follicles, and its expression level decreased following ovulatory hCG stimulus. Intra-bursal treatment with rosiglitazone (a PPARγ agonist) simultaneously with subcutaneously administered hCG blocked the induction of cyclooxygenase-2 and steroidogenic acute regulatory protein (StAR) in preovulatory follicles. Consistently, tissue levels of their respective products, prostaglandin (PG) E₂ and progesterone (P4), were reduced, leading to significantly decreased ovulation rate. GW9662, a PPARγ antagonist, was almost ineffective to alter those values. Local treatment with rosiglitazone 24 hr after hCG administration caused reductions in the size, StAR expression and P4 secretion of corpus luteum 48 hr later. Obtained data are possible functional evidence with rats for granulosa cell PPARγ as a negative regulator of PG and P4 synthesis during follicle rupture and transformation to luteal tissue. LH/hCG-induced decreases in PPARγ expression and its activity would be an early component in the proper induction of following ovulatory cascade and luteal development.