| peroxisome proliferator activated receptor gamma | OKDB#: 369 |
| Symbols: | PPARG | Species: | human | ||
| Synonyms: | GLM1, CIMT1, NR1C3, PPARG1, PPARG2, PPARG5, PPARgamma | Locus: | 3p25.2 in Homo sapiens | HPMR |
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| General Comment |
The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors. PPARs form heterodimers with retinoid X receptors and these heterodimers regulate transcription of various genes. There are 3 known subtypes of PPARs, PPAR-alpha, PPAR-delta, and PPAR-gamma. PPAR-gamma is believed to be involved in adipocyte differentiation. Elbrecht et al. (1996) cloned cDNAs of PPAR-gamma-1 and PPAR-gamma-2 from human fat cell cDNA by PCR using primers based on the mouse sequence. They found that the human PPAR-gamma-1 and PPAR-gamma-2 genes have identical sequences except that PPAR-gamma-2 contains an additional 84 nucleotides at its 5-prime end.
NCBI Summary: This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008] |
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| General function | Receptor, Nucleic acid binding, DNA binding, Transcription factor | ||||
| Comment | The thiazolidinediones are synthetic compounds that can normalize elevated plasma glucose levels in obese, diabetic rodents and may be efficacious therapeutic agents for the treatment of noninsulin-dependent diabetes mellitus. Lehmann et al. (1995) identified the thiazolidinediones as high affinity ligands for mouse PPAR-gamma receptors. Elbrecht et al. (1996) confirmed that human PPAR-gamma-1 and PPAR-gamma-2 have similar activity and determined that 3 different thiazolidinedione compounds are agonists of PPAR-gamma-1 and PPAR-gamma-2. Elbrecht et al. (1996) speculated that the antidiabetic activity of the thiazolidinediones in humans is mediated through the activation of PPAR-gamma-1 and PPAR-gamma-2. | ||||
| Cellular localization | Nuclear | ||||
| Comment | candidate123. | ||||
| Ovarian function | Follicle development, Initiation of primordial follicle growth, Cumulus cell differentiation, Ovulation, Steroid metabolism, Luteinization, Oocyte maturation | ||||
| Comment | Peroxisome Proliferator-Activated Receptor Gamma Modulator Promotes Neonatal Mouse Primordial Follicle Activation In Vitro. Yoon SY et al. (2020) Peroxisome proliferator-activated receptor gamma (PPARγ) is known as a regulator of cellular functions, including adipogenesis and immune cell activation. The objectives of this study were to investigate the expression of PPARγ and identify the mechanism of primordial follicle activation via PPARγ modulators in mouse ovaries. We first measured the gene expression of PPARγ and determined its relationship with phosphatase and tensin homolog (PTEN), protein kinase B (AKT1), and forkhead box O3a (FOXO3a) expression in neonatal mouse ovaries. We then incubated neonatal mouse ovaries with PPARγ modulators, including rosiglitazone (a synthetic agonist of PPARγ), GW9662 (a synthetic antagonist of PPARγ), and cyclic phosphatidic acid (cPA, a physiological inhibitor of PPARγ), followed by transplantation into adult ovariectomized mice. After the maturation of the transplanted ovaries, primordial follicle growth activation, follicle growth, and embryonic development were evaluated. Finally, the delivery of live pups after embryo transfer into recipient mice was assessed. While PPARγ was expressed in ovaries from mice of all ages, its levels were significantly increased in ovaries from 20-day-old mice. In GW9662-treated ovaries in vitro, PTEN levels were decreased, AKT was activated, and FOXO3a was excluded from the nuclei of primordial follicles. After 1 month, cPA-pretreated, transplanted ovaries produced the highest numbers of oocytes and polar bodies, exhibited the most advanced embryonic development, and had the greatest blastocyst formation rate compared to the rosiglitazone- and GW9662-pretreated groups. Additionally, the successful delivery of live pups after embryo transfer into the recipient mice transplanted with cPA-pretreated ovaries was confirmed. Our study demonstrates that PPARγ participates in primordial follicle activation and development, possibly mediated in part by the PI3K/AKT signaling pathway. Although more studies are required, adapting these findings for the activation of human primordial follicles may lead to treatments for infertility that originates from poor ovarian reserves.////////////////// Expression of the genes for peroxisome proliferator-activated receptor-γ, cyclooxygenase-2, and proinflammatory cytokines in granulosa cells from women with polycystic ovary syndrome. Lee JY et al. (2017) To identify differences in the expression of the genes for peroxisome proliferator-activated receptor (PPAR)-γ, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. PPAR-γ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p=0.034 and p=0.018, respectively), but the expression of IL-6 and TNF-α mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the PPAR-γ, COX-2, IL-6, and TNF-α mRNA levels. Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of PPAR-γ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.////////////////// Modulating Intrafollicular Hormonal Milieu in Controlled Ovarian Stimulation: Insights from PPAR Expression in Human Granulosa Cells. Tatone C et al. (2015) Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors relevant to steroid metabolism in granulosa cells (GCs). We investigated whether PPARs and their steroidogenic targets were differentially expressed in GCs differentiated under different recombinant or urinary gonadotropin preparations. GCs from women subjected to COS with r-hFSH, r-hFSH/r-hLH or hMG-HP were processed to assess expression of PPARα, PPARβ/δ, PPARγ and steroidogenic enzymes under PPAR modulation. As an evidence of their activation, all PPAR isotypes with their coactivators, the retinoic-X-receptors (RXRs), localized in the nucleus. When GCs from r-hFSH/r-hLH group were compared with r-hFSH, a significant reduction of PPARα protein was observed. By contrast, an increase of PPARβ/δ at both protein and mRNA levels along with that of PPARγ protein were detected. The steroidogenic enzymes 17βHSD IV, 3βHSD II and HMG-CoA red were downregulated in the r-hFSH/r-hLH group in comparison to r-hFSH unlike CYP19A1 that remained unchanged. In GCs from urinary FSH-LH stimulation (hMG-HP), PPARα was more expressed in comparison with r-hFSH/r-hLH group. Likewise, 3βHSD II and 17βHSD IV were increased suggesting that hMG-HP partially mimicked r-hFSH/r-hLH effects. In summary, transcript analysis associated to protein investigation revealed differential effects of COS protocols on PPARs and their steroidogenic targets in relation to LH and gonadotropin source. These observations candidate PPARs as new biomarkers of follicle competence opening new hypotheses on COS effects on ovarian physiology. This article is protected by copyright. All rights reserved.////////////////// Regulation of Fatty Acid Oxidation in Mouse Cumulus-Oocyte Complexes during Maturation and Modulation by PPAR Agonists. Dunning KR 2014 et al. Fatty acid oxidation is an important energy source for the oocyte; however, little is known about how this metabolic pathway is regulated in cumulus-oocyte complexes. Analysis of genes involved in fatty acid oxidation showed that many are regulated by the luteinizing hormone surge during in vivo maturation, including acyl-CoA synthetases, carnitine transporters, acyl-CoA dehydrogenases and acetyl-CoA transferase, but that many are dysregulated when cumulus-oocyte complexes are matured under in vitro maturation conditions using follicle stimulating hormone and epidermal growth factor. Fatty acid oxidation, measured as production of (3)H2O from (3)H]palmitic acid, occurs in mouse cumulus-oocyte complexes in response to the luteinizing hormone surge but is significantly reduced in cumulus-oocyte complexes matured in vitro. Thus we sought to determine whether fatty acid oxidation in cumulus-oocyte complexes could be modulated during in vitro maturation by lipid metabolism regulators, namely peroxisome proliferator activated receptor (PPAR) agonists bezafibrate and rosiglitazone. Bezafibrate showed no effect with increasing dose, while rosiglitazone dose dependently inhibited fatty acid oxidation in cumulus-oocyte complexes during in vitro maturation. To determine the impact of rosiglitazone on oocyte developmental competence, cumulus-oocyte complexes were treated with rosiglitazone during in vitro maturation and gene expression, oocyte mitochondrial activity and embryo development following in vitro fertilization were assessed. Rosiglitazone restored Acsl1, Cpt1b and Acaa2 levels in cumulus-oocyte complexes and increased oocyte mitochondrial membrane potential yet resulted in significantly fewer embryos reaching the morula and hatching blastocyst stages. Thus fatty acid oxidation is increased in cumulus-oocyte complexes matured in vivo and deficient during in vitro maturation, a known model of poor oocyte quality. That rosiglitazone further decreased fatty acid oxidation during in vitro maturation and resulted in poor embryo development points to the developmental importance of fatty acid oxidation and the need for it to be optimized during in vitro maturation to improve this reproductive technology. ///////////////////////// Evidence for a Luteotropic Role of Peroxisome Proliferator-Activated Receptor Gamma: Expression and In Vitro Effects on Enzymatic and Hormonal Activities in Corpora Lutea of Pseudopregnant Rabbits. [Zerani M et al. The expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and its role in corpora lutea (CL) function were studied in pseudopregnant rabbits. CL were collected at early (Day 4), mid (Day 9), and late (Day 13) stages of pseudopregnancy. Immunohistochemistry evidenced the presence of PPARgamma in the perinuclear cytoplasm and nucleus of all luteal cells; immunoreactivity decreased from early to late stage, with immunonegativity of the nuclei of late CL. PPARgamma mRNA transcript was expressed in all luteal stages with the lowest level at late stage. In CL cultured in vitro, PPARgamma agonist (15-deoxy delta12,14 prostaglandin J2, 15d-PGJ2, 200 nM) increased and antagonist (T0070907, 50 nM) decreased progesterone secretion at early and mid luteal stages, whereas 15d-PGJ2 reduced and T0070907 increased PGF2alpha ones. Prostaglandin-endoperoxide synthase 2 (PTGS2) activity was reduced by 15d-PGJ2 and increased by T0070907 in corpora lutea of early and mid luteal stages. Conversely, 15d-PGJ2 increased and T0070907 reduced 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in early and mid luteal stage CL. PGE2 in vitro secretion as well as PTGS1 and 20alpha-HSD enzymatic activities were not affected by 15d-PGJ2 and T0070907 in any CL types. These results indicate that PPARgamma plays a luteotropic role in pseudopregnant rabbits, through PTGS2 down-regulation and 3beta-HSD up-regulation, with consequent PGF2alpha decrease and progesterone increase.As peroxisome proliferator-activated receptors (PPARs) play a role in cholesterol and lipid metabolism, Lohrke et al showed the expression of PPARgamma in bovine lutein cells (day 12 of the ovarian cycle) at the mRNA and protein level by imaging, flow cytometry and blot analysis, and a role of PPARgamma in the secretion of progesterone. The cells (24 h culture) responded dose dependently by increasing progesterone secretion (up to 1.5-fold of the basal level) to an endogenous ligand of PPARgamma, 15-deoxy-delta12,14 prostaglandin J2 (15-dPGJ2) and to the thiazolidinedione ciglitizone. Aurintricarboxylic acid (ATA) was found to reduce the intracellular PPARgamma level and to promote cell cycle progress, indicating that ATA can be used as a tool for experimental changes of PPARgamma proteins in intact cells and for studying the physiological consequences. The ATA-mediated decrease of PPARgamma was accompanied by reduced progesterone production and a progression of the cell cycle, suggesting a function of PPARgamma in both processes. Froment P, et al. (Biol Reprod. 2003) also reported that peroxisome proliferator-activated receptor-gamma expresses and functions in ovarian folliculogenesis in the sheep. Role of PPARgamma and its gonadotrophic regulation in rat ovarian granulosa cells in vitro. Zhang H et al. The peroxisome proliferator-activated receptors (PPARs), including PPARalpha, PPARbeta/delta, and PPARgamma, are a family of transcription factors belonging to the steroid receptor superfamily. In rat ovary, PPARgamma is mainly expressed in granulosa cells of developing follicles, implying a possible role of PPARgamma in ovarian functions. In the present study, the role of PPARgamma and its gonadotrophic regulation in granulosa cells collected from diethylstilbestrol-treated immature rats were studied. The results showed that PPARgamma could inhibit proliferation and induce apoptosis in primarily cultured granulosa cells. PPARgamma could also stimulate the biosynthesis of estradiol and progesterone after FSH pretreatment, and FSH could regulate the functions of PPARgamma through PKA, ERK1/2, and p38 MAPK signaling pathways. These data suggested that PPARgamma may be involved in follicular atresia and FSH-stimulated steroidogenesis during follicle development. | ||||
| Expression regulated by | LH, mir27b | ||||
| Comment | PPARγ is regulated by miR-27b-3p negatively and plays an important role in porcine oocyte maturation. Song C et al. (2016) To elucidate the key miRNAs and the signalling pathways that are involved in porcine oocyte maturation, we performed a deep sequencing analysis of the miRNAs of pig germinal vesicle (GV) oocytes and metaphase II (MII) oocytes. Seven differentially expressed (DE) miRNAs were identified and the expression levels of miR-21 and miR-27b-3p were further confirmed by QPCR analysis. The target genes of 7 DE miRNAs were predicted and subjected to pathway analysis. Interestingly, fatty acid metabolism and fatty acid biosynthesis were the top two significantly enriched molecular functions during oocyte maturation. Heat map, which was built with 7 DE miRNAs and the enriched the molecular functions, revealed that miR-21, miR-27b-3p, miR-10a-5p and miR-10b-5p were involved in fatty acid metabolism. In particular, the regulatory role of miR-27b-3p on peroxisome proliferator-activated receptor-γ (PPARγ) was confirmed by their inversed expression patterns in GV and MII oocytes and luciferase report assays. In addition, we observed that PPARγ agonist (rosiglitazone) treatment significantly enhanced porcine oocyte maturation rate and early embryo developmental competent. Taken together, our results demonstrated that miR-27b and its target, PPARγ, play the vital roles in pig oocyte maturation through regulating the fatty acid metabolism. These data increased our understanding of the regulatory gene networks in porcine oocyte maturation and development.////////////////// hCG-Induced Down-Regulation of PPAR{gamma} and Liver X Receptors Promotes Periovulatory Progesterone Synthesis by Macaque Granulosa Cells. Puttabyatappa M et al. An ovulatory stimulus induces the rapid and dramatic increase in progesterone synthesis by the primate ovarian follicle. However, little is known about the early events leading to the shift from estrogen to progesterone production. Because steroidogenesis represents an aspect of cholesterol metabolism, it was hypothesized that transcription factors regulating cholesterol balance would be among the earliest to change in response to an ovulatory stimulus. Granulosa cells were isolated from rhesus monkey follicles following controlled ovarian stimulation protocols before or up to 24 hr after an ovulatory human chorionic gonadotropin (hCG) bolus. The peroxisome proliferator-activated receptor-? (PPARG) and the liver X receptors nuclear receptor (NR)1H2, NR1H3] decreased within 3 hr of hCG, as did the reverse cholesterol transporters ATP-binding cassette (ABC)A1 and ABCG1. Treatment of granulosa cells isolated before an ovulatory stimulus with hCG and rosiglitizone resulted in an increase in NR1H3 and ABCG1, and decreased steroidogenic acute regulatory (STAR) protein and scavenger receptor-BI (SCARB1). A liver X receptor agonist attenuated hCG-induced progesterone synthesis in vitro and increased the expression of ABCA1 and ABCG1, and suppressed STAR, P450 side-chain cleavage A1, hydroxysteroid dehydrogenase 3B, and SCARB1. These data suggest that an initial action of LH/CG on the primate preovulatory follicle is to rapidly reduce the expression of PPARG, resulting in reduced NR1H3 with the consequence shifting the balance from cholesterol efflux via ABCA1 and ABCG1 to cholesterol uptake (SCARB1) and metabolism (STAR, P450 side-chain cleavage A1, hydroxysteroid dehydrogenase 3B). That the regulation of PPARG and the liver X receptors occurs within 3 hr strongly indicates that early events in the primate luteinizing follicle are critical to successful ovulation and luteal formation. [Orio F Jr, et al reported the Exon 6 and 2 Peroxisome Proliferator-Activated Receptor-gamma Polymorphisms in Polycystic Ovary Syndrome. Obesity affects about 44% of women with polycystic ovary syndrome (PCOS). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is one of the genes involved in the differentiation of adipose tissue. In an attempt to shed light on the high percentage of obesity in PCOS, we examined polymorphisms at exons 6 and 2 of the PPAR-gamma gene in 100 PCOS patients and in 100 healthy controls matched for age and body mass index (BMI). The T allele frequency of exon 6 was significantly higher (P < 0.05) in PCOS patients compared with control women. In addition, the BMI and leptin levels were significantly higher (P < 0.05) in PCOS patients carrying the C-->T substitution than in controls. There was no significant difference in leptin levels after normalization for BMI. The Pro(12)Ala polymorphism at exon 2 was unrelated to BMI and/or leptin levels in PCOS women. In conclusion, the higher frequency of the C-->T substitution in exon 6 of the PPAR-gamma gene in PCOS women suggests that it plays a role in the complex pathogenetic mechanism of obesity in PCOS, whereas the Pro(12)Ala polymorphism does not seem to affect BMI in PCOS women. Effects of luteinizing hormone on peroxisome proliferator-activated receptor {gamma} in the rat ovary before and after the gonadotropin surge Banerjee J, et al . We have shown previously that mRNA for peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in granulosa cells and downregulated by the luteinizing hormone (LH) surge. The current studies were undertaken to test the hypothesis that LH stimulates a decrease in the expression of PPARgamma, as well as its activity, in granulosa cells. Ovaries were collected from immature rats 0 and 48 h after they received pregnant mares' serum gonadotropin (PMSG), and 4 and 24 h after administration of human chorionic gonadotropin (hCG), and used for protein isolation or processed for immunolocalization of PPARgamma. The amount of phosphorylated PPARgamma was measured by immunoblot analysis to determine how LH affects the phosphorylation status, and therefore the activity, of PPARgamma. Granulosa cells were also collected from immature rats 48 h after PMSG. Cells were cultured with LH in the absence and presence of H89 and cycloheximide to investigate the role of PKA and protein synthesis in the LH-mediated decline in mRNA for PPARgamma respectively. Protein corresponding to PPARgamma was localized to nuclei of granulosa cells 0 and 48 h after PMSG. Expression was greatly reduced by 4 h after hCG, with expression in mural granulosa cells lost before that in cumulus cells. The amount of phosphorylated PPARgamma did not change during the periovulatory period. Blocking PKA activity had no effect on levels of mRNA for PPARgamma. However, levels of mRNA for PPARgamma were significantly increased in cells treated with cycloheximide (P < 0.05, ANOVA followed by Tukey's Hsd). These data suggest that PPARgamma is tightly regulated in the ovary and that its expression is the primary mechanism by which LH influences the activity of PPARgamma. In addition, protein synthesis may be involved in modulating levels of PPARgamma in granulosa cells. Initiation of the expression of peroxisome proliferator - activated receptor gamma (PPAR gamma) in the rat ovary and the role of FSH. Long MJ et al. ABSTRACT: PPARgamma is highly expressed in granulosa cells by 23 days post-partum (pp) and is down-regulated in response to the LH surge. We tested the hypothesis that high levels of FSH during the neonatal period trigger the expression of PPARgamma. To determine when PPARgamma expression is initiated, ovaries were collected from neonatal rats. Messenger RNA for PPARgamma was undetectable on day 1, low from days 5-14, and increased by day 19 pp (p<0.05). PPARgamma was detected in select granulosa cells in primary/early secondary follicles. Messenger RNA for the FSH receptor was detected as early as day 1 and remained steady throughout day 19 pp. The FSH receptor was detected by immunoblot analysis in ovaries collected 1, 2, and 5-9 days pp. In a subsequent experiment, neonatal rats were treated with acyline (GnRH antagonist) which significantly reduced FSH (p<0.05) but not levels of mRNA for PPARgamma. The role of FSH in the induction of PPARgamma expression was further assessed in ovarian tissue from FORKO mice. Both mRNA and protein for PPARgamma were identified in ovarian tissue from FORKO mice. In summary, the FSH/FSH receptor system is present in granulosa cells prior to the onset of expression of PPARgamma. Reducing FSH during the neonatal period, or the ability to respond to FSH, did not decrease expression of mRNA for PPARgamma. These data indicate that FSH is not a primary factor initiating the expression of PPARgamma and that other agents play a role in activating its expression in the ovary. | ||||
| Ovarian localization | Oocyte, Granulosa, Luteal cells | ||||
| Comment | Expression of the genes for peroxisome proliferator-activated receptor-γ, cyclooxygenase-2, and proinflammatory cytokines in granulosa cells from women with polycystic ovary syndrome. Lee JY et al. (2017) To identify differences in the expression of the genes for peroxisome proliferator-activated receptor (PPAR)-γ, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. PPAR-γ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p=0.034 and p=0.018, respectively), but the expression of IL-6 and TNF-α mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the PPAR-γ, COX-2, IL-6, and TNF-α mRNA levels. Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of PPAR-γ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.////////////////// The distribution of PPAR gamma mRNAs in various bovine tissues was investigated using Northern blot analysis by Sundvold et al . The highest expression was detected in adipose tissue with about equal amounts of the both gamma 1 and gamma 2 transcripts while a differential expression was found in other tissues investigated. PPAR gamma 1 was expressed at relatively high levels in bovine spleen and lung and to a lower extent in ovary, mammary gland, and small intestine. The amount of PPAR gamma 2 was apparently lower than that of PPAR gamma 1 in spleen, lung, and ovary. Komar CM et al 2001 et al reported the expression and localization of PPARs in the rat ovary during follicular development and the periovulatory period. Lovekamp-Swan T, et al.(Mol Cell Endocrinol. 2003) also believed that MEHP activates both PPARalpha and PPARgamma to suppress aromatase and alter other genes related to metabolism and differentiation in the granulosa cell. | ||||
| Follicle stages | Preovulatory, Corpus luteum | ||||
| Comment | Lambe et al have cloned a human cognate of the mouse peroxisome-proliferator-activated receptor-gamma (hPPAR gamma) from a human placenta cDNA library. Sequence analysis reveals a high degree of similarity with the mouse receptor and, like other PPAR, hPPAR gamma forms heterodimers with the retinoid X receptor alpha (RXR alpha) and binds in vitro to DNA elements containing direct repeats of the sequence TGACCT. In common with mouse PPAR gamma, hPPAR gamma is expressed strongly in adipose tissue, but significant levels also are detectable in placenta, lung and ovary. Mu YM, et al 2000 reported that insulin sensitizer, troglitazone, directly inhibits aromatase activity in human ovarian granulosa cells. The effects of Tro and/or RXR ligand, LG100268 (LG) on the aromatase activity was examioned in cultured human ovarian granulosa cells obtained from patients who underwent in vitro fertilization. Human ovarian granulosa cells expressed PPAR gamma mRNA assessed by RT-PCR. The treatment of the granulosa cells with Tro for 24 h resulted in a dramatic inhibition of the aromatase activity in a dose-dependent manner, While the treatment with LG alone also inhibited the aromatase activity, the combined treatment with both Tro and LG caused a much more reduction in the aromatase activity. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene in women with polycystic ovary syndrome. Yilmaz M et al. Aim. The present study was designed to examine the relationship between Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene (PPAR-gamma) and clinical and hormonal characteristics in women with polycystic ovary syndrome (PCOS).Materials and methods. One hundred patients with PCOS and 100 healthy subjects were included in the study. Serum levels of sex steroids were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). The responses of glucose and insulin to an oral glucose tolerance test were analyzed by calculating the respective area under the curve (AUC) by the trapezoidal method. We used the restriction fragment length polymorphism technique and polymerase chain reaction to examine Pro12Ala polymorphism in exon 2 of PPAR-gamma.Results. Pro12Ala polymorphism of PPAR-gamma was significantly elevated in control subjects (22%) compared with PCOS subjects (15%). All of the Pro12Ala polymorphisms of PPAR-gamma were heterozygous. When PCOS subjects with the Pro allele and the Ala allele of PPAR-gamma were compared, the latter had lower free testosterone, androstenedione, dehydroepiandrosterone sulfate, insulin and C-peptide levels, as well as lower luteinizing hormone/follicle-stimulating hormone ratio, HOMA insulin resistance index, AUCinsulin, Ferriman-Gallwey score, acne, body mass index and waist-to-hip ratio.Conclusion. We suggest that Pro12Ala polymorphism of the PPAR-gamma gene may be a modifier of insulin resistance in women with PCOS. | ||||
| Phenotypes |
PCO (polycystic ovarian syndrome) |
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| Mutations |
12 mutations
Species: human
Species: mouse
Species: mouse
Species: mouse
Species: human
Species: human
Species: human
Species: human
Species: human
Species: human
Species: human
Species: human
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
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