The Biological Actions of Dehydroepiandrosterone Involves Multiple Receptors

Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the peroxisome proliferators activated receptor alpha, pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated leading to additional mechanisms by which DHEA may exert its biological effects. This review will provide an overview of the receptor multiplicity involved in the biological activity of this sterol.     

Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer

Because the peroxisome proliferator-activated receptor (PPAR) signaling pathway is involved in development and progression of pancreatic cancer, we investigated associations between genetic variants of the PPAR pathway genes and pancreatic cancer risk by using three published genome-wide association study datasets including 8477 cases and 6946 controls of European ancestry. Expression quantitative trait loci (eQTL) analysis was also performed for correlations between genotypes of the identified genetic variants and messenger RNA (mRNA) expression levels of their genes by using available databases of the 1000 Genomes, TCGA, and GTEx projects. In the single-locus logistic regression analysis, we identified 1141 out of 17 532 significant single-nucleotide polymorphisms (SNPs) in 112 PPAR pathway genes. Further multivariate logistic regression analysis identified three independent, potentially functional loci (rs12947620 in MED1, rs11079651 in PRKCA, and rs34367566 in PRKCB) for pancreatic cancer risk (odds ratio [OR] = 1.11, 95% confidence interval [CI], [1.06-1.17], P = 5.46 × 10⁻⁵; OR = 1.10, 95% CI, [1.04-1.15], P = 1.99 × 10⁻⁴; and OR = 1.09, 95% CI, [1.04-1.14], P = 3.16 × 10⁻⁴, respectively) among 65 SNPs that passed multiple comparison correction by false discovery rate (< 0.2). When risk genotypes of these three SNPs were combined, carriers with 2 to 3 unfavorable genotypes (NUGs) had a higher risk of pancreatic cancer than those with 0 to 1 NUGs. The eQTL analysis showed that rs34367566 A>AG was associated with decreased expression levels of PRKCB mRNA in 373 lymphoblastoid cell lines. Our findings indicate that genetic variants of the PPAR pathway genes, particularly MED1, PRKCA, and PRKCB, may contribute to susceptibility to pancreatic cancer.     

PPARγ在子宫内膜异位症中的作用研究进展

现有的研究已阐明激活PPARγ具有抑制炎症反应、抗血管生成等作用,而炎症反应和血管生成均参与了子宫内膜异位症的发生发展,并且PPARγ在正常子宫内膜组织及异位子宫内膜组织均有表达。PPARγ在子宫内膜异位症中的作用受到越来越多的关注,该文就PPARγ在子宫内膜异位症中的意义作一综述。