Abstract Dysfunction in regulatory T-cells (Tregs) is a hallmark of autoimmune hepatitis (AIH), serious hepatopathy often leading to end-stage liver damage and transplantation, if not treated. Treg impairment AIH has been linked defective response aryl hydrocarbon receptor (AhR) activation. AhR acts as modulator toxin adaptive immunity. We have previously shown that altered Tregs activation der...

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxy...

Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive functions in rats and mice. IGF-1 expression is regulated by estrogen in several reproductive organs including the uterus and ovary. Two types of estrogen receptor (ERα and ERβ) are expressed in mouse uteri and ovaries, and it is unclear whether they differently mediate IGF-1 gene transcription. To clarify the roles...

AIMS Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial ...

Estrogen receptors (ERs) are important for preventing endotoxin-induced myocardial dysfunction. Therefore, plant-derived phytoestrogens, which target ERs may also affect endotoxin-induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside-R1 (NG-R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG-R1 ...

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase. ADMA accumulation, mainly due to a decreased dimethylarginine dimethylaminohydrolase (DDAH) activity, has been related to the development of cardiovascular diseases. We investigate whether estradiol prevents the changes induced by oxidized low density lipoprotein (oxLDL) on the DDAH/ADMA/NO pathway in h...

Estrogen affects mitochondrial function in various tissues, but the precise mechanism remains unclear. We, therefore investigated the effect on estrogen-regulated mitochondrial morphology by dynamin-related protein 1 (Drp1) and its Ser616-phosphorylated derivative (pDrp1Ser616) are involved in mitochondrial fission. MCF7 human breast cancer cells were treated with 17β-estradiol (E2), an estroge...

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding d...

Physiological concentrations of the green tea extract epigallocatechin-3-gallate (EGCG) caused growth inhibition in estrogen receptor α (ERα)-positive MCF7 cells that was associated with down-regulation of the ERα and reduced insulin-like growth factor binding protein-2 abundance and increased protein abundance of the tumor suppressor genes p53/p21. In contrast to MCF7 cells that have wt p53, E...

Estrogen receptor (ER) antagonists are generally thought to inhibit estrogen action through competitive inhibition, resulting in receptor binding to antagonist rather than agonist. However, microarray analyses reveal a group of genes for which ER agonist and antagonist cooperatively regulate expression, suggesting additional models of combined agonist/antagonist action must exist. In conjunctio...