Stanford Home
Ovarian Kaleidoscope Database (OKdb)

Home

History

Transgenic Mouse Models

INFORGRAPHICS

Search
Submit
Update
Chroms
Browse
Admin

Hsueh lab

HPMR

Visits
since 01/2001:
176557

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA; PPARA OKDB#: 1341
 Symbols: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA; Species: human
 Synonyms: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR, PPAR|  Locus: 22q12-q13.1 in Homo sapiens
HPMR


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
Mammalian Reproductive Genetics   Endometrium Database Resource   Orthologous Genes   UCSC Genome Browser   GEO Profiles new!   Amazonia (transcriptome data) new!

R-L INTERACTIONS   MGI

DNA Microarrays
SHOW DATA ...
link to BioGPS
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.

NCBI Summary: Peroxisome proliferators are a diverse group of chemicals which include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers, and are so called because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals, and contain enzymes for respiration, cholesterol and lipid metabolism. Infact, the fibrate class of hypolipidemic drugs is used to reduce triglycerides and cholesterol in patients with hyperlipidemia, a major risk factor for coronary heart disease. The action of peroxisome proliferators is thought to be mediated via specific receptors belonging to the steroid hormone receptor superfamily, called PPARs. Thus far, four closely related subtypes, alpha, beta, gamma and delta, have been identified. The subtype PPAR-alpha, encoded by PPARA, is a nuclear transcription factor. Upon activation by peroxisome proliferators, it modulates the expression of target genes involved in lipid metabolism, suggesting a role for PPAR-alpha in lipid homeostasis.
General function Receptor, DNA binding, Transcription factor
Comment
Cellular localization Nuclear
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization Granulosa, Theca, 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 Lovekamp-Swan T, et al reported the dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Peroxisome proliferator-activated receptors (PPARs) are key regulators of lipid metabolism and cell differentiation. The plasticizer di-(2-ethylhexyl) phthalate is a peroxisome proliferator, and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) activates PPARalpha and PPARgamma in cell transactivation assays. MEHP is a female reproductive toxicant and decreases activity, mRNA, and protein levels of aromatase, the rate-limiting enzyme that converts testosterone to estradiol in ovarian granulosa cells. To test the hypothesis that MEHP suppresses aromatase through PPAR pathways, granulosa cells were cultured with MEHP (50 &mgr;M) or selective activators of PPARgamma or PPARalpha for 48 h and gene expression was analyzed by real time RT-PCR. Both PPARalpha and PPARgamma activators significantly decreased aromatase mRNA and estradiol production like MEHP. The PPARgamma-selective antagonist GR 259662 partially blocked the suppression of aromatase by MEHP, suggesting that MEHP acts through PPARgamma, but not exclusively. MEHP and the PPARalpha-selective agonist GW 327647 induced expression of 17beta-hydroxysteroid dehydrogenase IV, a known PPARalpha-regulated gene, and induction was maintained with addition of the PPARgamma-selective antagonist. PPARalpha-selective activation also induced expression of aryl hydrocarbon receptor (AhR), CYP1B1, and epoxide hydrolase in the granulosa cell. These data support a model in which MEHP activates both PPARalpha and PPARgamma to suppress aromatase and alter other genes related to metabolism and differentiation in the granulosa cell.
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
KEGG Pathways
Recent Publications
None
Search for Antibody


created: Oct. 23, 2001, 12:02 p.m. by: hsueh   email:
home page:
last update: April 23, 2003, 9:01 a.m. by: system    email:



Use the back button of your browser to return to the Gene List.

Click here to return to gene search form