Potential role for peroxisome proliferator-activated receptor gamma in regulating luteal lifespan in the rat.
Peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to stimulate progesterone production by bovine luteal cells. We previously reported higher expression of PPARgamma in old compared with new luteal tissue in the rat. The following studies were conducted to determine the role of PPARgamma in rat corpora lutea (CL) and test the hypothesis that PPARgamma 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 PPARgamma and P450 side-chain cleavage (SCC) was localized in luteal tissue by in situ hybridization, and protein corresponding to PPARgamma and macrophages identified by immunohistochemistry. Luteal tissue was cultured with agonists (ciglitazone, prostaglandin J2) or an antagonist (GW-9662) of PPARgamma. Progesterone was measured in media by RIA and levels of mRNA for 20alpha-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 PPARgamma. There was no effect of PPARgamma agonists or the antagonist on luteal progesterone production in vitro, or levels of mRNA for 20alpha-HSD. PPARgamma 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 PPARgamma is not a major player in luteal progesterone production or metabolism but may be involved in regulating luteal lifespan.
Tinfo
Nicole
N
Department of Animal Science, Iowa State University, Ames, Iowa 50011, USA.
Komar
Carolyn
C
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003338:Corpus Luteum / Q000378:metabolism*; D003340:Corpus Luteum Maintenance / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011555:Pseudopregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D046509:Tissue Culture Techniques
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D045162:Thiazolidinediones; C037112:9-deoxy-delta-9-prostaglandin D2; D002786:Cholesterol Side-Chain Cleavage Enzyme; D015230:Prostaglandin D2; C039671:ciglitazone