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.
NCBI Summary:
This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2017]
General function
Receptor, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
candidate123
Ovarian function
Follicle development, Luteinization
Comment
Pregnancy-associated changes of Peroxisome Proliferator-Activated Receptor Delta (PPARD) and Cytochrome P450 Family 21 Subfamily A Member 2 (CYP21A2) expression in the bovine corpus luteum. Sakumoto R et al. (2020) We investigated gene expression profiles of the corpus luteum (CL) at the time of maternal recognition to evaluate the functional changes of the CL during early pregnancy in cows and help improve reproductive efficiency and avoid defective fetuses. Microarray analyses using a 15 K bovine oligo DNA microarray detected 30 differentially expressed genes and 266 differentially expressed genes (e.g., PPARD and CYP21A2) in the CL on pregnancy days 15 (P15) and 18 (P18), respectively, compared with the CL on day 15 (NP15) of non-pregnancy (n = 4 for each group). PPARD expression was the highest while the CYP21A2 expression was the lowest in P15 and P18 compared with that of NP15. These microarray results were validated by quantitative real-time PCR analysis. The addition of interferon-τ (IFNT) and supernatants derived from homogenized fetal trophoblast (FMP) increased ISG15 and MX1 expressions in the cultured luteal tissue (P < 0.01), but did not affect PPARD and CYP21A2 expressions. PPARD expression in the luteal tissue was stimulated (P < 0.05) by GW0742, known as a selective PPARD agonist, and PPARD ligands (i.e., arachidonic, linoleic and linolenic acids). In contrast, CYP21A2 mRNA expression was not affected by both agonist and ligands. The concentration of prostaglandin (PG) E2 and PGF2α decreased after GW0742 stimulation and increased after arachidonic acid stimulation (P < 0.05). The addition of GW0742 and arachidonic acid increased progesterone (P4) concentration. Collectively, these findings suggest that high expression levels of PPARD and low expression levels of CYP21A2 in the CL during early pregnancy may support P4 production by bovine luteal cells.//////////////////
Expression regulated by
Comment
Ovarian localization
Theca, Luteal cells, Stromal cells
Comment
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.
PPARs are a family of nuclear hormone receptors involved in various processes
that could influence ovarian function. The authors investigated the cellular localization and
expression of PPARs during follicular development in ovarian tissue collected
from rats 0, 6, 12, 24, and 48 h post-PMSG. A second group of animals received
human CG (hCG) 48 h post-PMSG. Their ovaries were removed 0, 4, 8, 12, and
24 h post-hCG to study the periovulatory period. mRNAs corresponding to the
PPAR isotypes (alpha, delta, and gamma) were localized by in situ hybridization.
Changes in the levels of mRNA for the PPARs were determined by ribonuclease
protection assays. mRNAs
for PPARalpha and delta were located primarily in theca and stroma, and their
levels did not change during the intervals studied. These data suggest that PPARgamma is involved in follicular
development, has a negative influence on the luteinization of granulosa cells,
and/or regulates the periovulatory shift in steroid production. The more general
and steady expression of PPARs alpha and delta indicate that they may play a role
in basal ovarian function.
Follicle stages
Antral, Preovulatory
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: The role of genetic variation in peroxisome proliferator-activated receptors in the polycystic ovary syndrome (PCOS): an original case-control study followed by systematic review and meta-analysis of existing evidence. San-Millán JL et al. (2010) To study the association of polymorphisms in the genes encoding peroxisome proliferator-activated receptors (PPARs) with the polycystic ovary syndrome (PCOS). Case-control study and meta-analysis of published evidence. One hundred and sixty-one polycystic ovary syndrome patients and 113 non-hyperandrogenic women. Genotyping for PPAR-gamma coactivator-1 gene (PPARGC1A) Gly482Ser, PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -681C/G variants and systematic review of the literature using the Entrez-PubMed search engine, followed by meta-analysis whenever possible. Polycystic ovary syndrome patients carried the Gly482Ser variant in PPARGC1A more frequently than controls (72%vs. 58%, chi(2 )=( )5.54 P = 0.019), whereas carriers of the PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -681C/G variants were distributed similarly among both groups. The interaction between the PPARGC1A Gly482Ser and PPAR-delta-87T/C variants was also associated with PCOS (OR = 1.24, 95% CI 1.05-1.50, P = 0.008). The systematic review identified 31 studies addressing associations between PPARs variants and PCOS; meta-analysis was possible for nine studies focusing on the PPAR-gamma2 Pro12Ala variant. Although the individual studies did not reveal any statistically significant association, meta-analysis uncovered that carrying the PPAR-gamma2 Pro12Ala variant was associated with a reduced probability of having PCOS (OR = 0.77, 95% CI 0.61-0.96, P = 0.025), and that this association may be mediated by an effect on insulin sensitivity. Common polymorphisms in the PPARGC1A, PPAR-delta and PPAR-gamma2 loci are associated with PCOS.//////////////////