Potential role for peroxisome proliferator-activated receptor γ in regulating luteal lifespan in the rat

Abstract

Peroxisome proliferator-activated receptor g (PPARg) has been shown to stimulate progesterone production by bovine luteal cells. We previously reported higher expression of PPARg in old compared with new luteal tissue in the rat. The following studies were conducted to determine the role of PPARg in rat corpora lutea (CL) and test the hypothesis that PPARg plays a role in the metabolism of progesterone and/or luteal lifespan. Ovaries were removed from naturally cycling rats throughout the estrous cycle, and pseudopregnant rats. mRNA for PPARg and P450 side-chain cleavage (SCC) was localized in luteal tissue by in situ hybridization, and protein corresponding to PPARg and macrophages identified by immunohistochemistry. Luteal tissue was cultured with agonists (ciglitazone, prostaglandin J 2 ) or an antagonist (GW-9662) of PPARg. Progesterone was measured in media by RIA and levels of mRNA for 20a-hydroxysteriod dehydrogenase (HSD) and bcl-2 were measured in luteal tissue after culture by RT-PCR. An inverse relationship existed between the expression of mRNA for SCC and PPARg. There was no effect of PPARg agonists or the antagonist on luteal progesterone production in vitro, or levels of mRNA for 20a-HSD. PPARg protein was localized to the nuclei of luteal cells and did not correspond with the presence of macrophages. In new CL, ciglitazone decreased mRNA for bcl-2 on proestrus, estrus, and metestrus. Interestingly, GW-9662 also decreased mRNA for bcl-2 on proestrus and diestrus in old and new CL, and on metestrus in new CL. These data indicate that PPARg is not a major player in luteal progesterone production or metabolism but may be involved in regulating luteal lifespan.

Expression and regulation of adipocyte fatty acid binding protein in granulosa cells and its relation with clinical characteristics of polycystic ovary syndrome

“…Evidence suggests that FABP4 expression is regulated by PPARc through the PPRE element presented in the FABP4 gene promoter [26]. PPARc is located in the nucleus of luteal cells where it may affect luteal cell survival via regulating the expression of bcl-2 [27]. Moreover, PPARc agonist rosiglitazone, either through systemic improvements to specific metabolic parameters or by direct modulation of PPARc-regulated gene expression (CD36, FABP4) in ovarian cells, is able to reverse the deficits in oocyte quality resulted from DIO [28].…”

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

“…PPARg agonists enhanced P 4 production in bovine luteal cells collected during mid-luteal phase of the estrous cycle [42] or by corpora lutea explants of pseudopregnant rabbits [21]. However, there was no effect of PPARg ligands on P 4 production in hemisected and cultured rat CL [32]. Our recent results indicate that PPAR (a, b, g) activators reduced P 4 secretion by the CL explants during early stages (days 10-12 and 14-16) of pregnancy, whereas they were ineffective during the corresponding days of the estrous cycle [43].…”

“…In turn, in rodent luteal and granulosa cells vitality was modulated by the regulation of anti-apoptotic bcl-2 protein and tumor suppressor p53 expression [31,32]. PPARs may affect the expression and activity of proteases and angiogenic factors which are engaged in the tissue remodeling and the formation of follicular or luteal cells.…”

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

“…Furthermore, another line of studies has been focusing on expression and role(s) of PPARγ in CL formed from a ruptured follicle. A low but notable level of PPARγ mRNA expression was negatively correlated with steroidogenic activity and a steroidogenic enzyme, P450 side chain cleavage (P450scc), mRNA in rat CL [10, 11, 32]. On the other hand, PPARγ protein expression in luteal cells decreased with aging in both non-pregnant and pregnant cow [34] and pseudopregnant rabbit [20] and was down-regulated by luteolytic PGF 2 α action [34].…”

“…On the other hand, PPARγ protein expression in luteal cells decreased with aging in both non-pregnant and pregnant cow [34] and pseudopregnant rabbit [20] and was down-regulated by luteolytic PGF 2 α action [34]. The impacts of natural (15d-PGJ 2 ) or synthetic (rosiglitazone) ligands of PPARγ on luteal P4 synthesis have so far been reported to be positive in bovine luteal cells in vitro [18] and in pseudopregnant rabbit CL in vitro [20], none in rat CL in vitro [32] or negative in porcine CL during early pregnancy [17]. Thus, data available are conflicting on the expression and definite functional role(s) of PPARγ in ovulatory follicles and subsequently formed CL.…”