Search results for "Estrogen"

Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38.

2007

Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-beta estradiol (0.2 nm) or with nutritionally relevant concentrations of genistein (0.5 microm), and 48 h later treated with 5 microm of amyloid beta (Abeta) for 24 h. We found that Abeta increased oxidative stress, measured as peroxide levels or oxidized glutathione/reduced glutathione ratio, which in turn, caused phosphorylation of p38 MAP kinase. Amyloid beta subsequently induced neuronal death. Inhibiting the MAP kinase pathway prevented cell death, confirming the role of …

Modulation of longevity-associated genes by estrogens or phytoestrogens.

2008

Abstract Females live longer than males. We have shown that the higher levels of estrogens in females protect them against aging, by up-regulating the expression of antioxidant, longevity-related genes, such as that of selenium-dependent glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). Both estradiol and genistein (the most abundant phytoestrogen in soybeans) share chemical properties which confer antioxidant features to these compounds. However, the low concentration of estrogens and phytoestrogens make it unlikely that they exhibit significant antioxidant capacity in the organism. Physiological concentrations of estrogens and nutritionally relevant concentrations of geni…

Ruolo degli estrogeni nella malattia di Parkinson

2007

Detection of a synthetic sex steroid in the American crocodile (Crocodylus acutus): Evidence for a novel environmental androgen

2017

Endocrine-disrupting contaminants (EDC's) are well known to alter sexual differentiation among vertebrates via estrogenic effects during development, particularly in organisms characterized by temperature-dependent sex determination. However, substances producing androgenic effects typically lack potency when tested in laboratory settings and are virtually unstudied in field settings. Here, we assay levels of a synthetic androgen, 17a-methyltestosterone (MT), in a heavily male-biased population of American crocodiles in the Tempisque River Basin of Costa Rica based on the recent hypothesis that this chemical is an EDC in developing crocodilian embryos. The presence of MT was documented in a…

Sex Differences in Age-Associated Type 2 Diabetes in Rats—Role of Estrogens and Oxidative Stress

2019

Females live longer than males, and the estrogens are one of the reasons for this difference. We reported some years ago that estrogens are able to protect rats against oxidative stress, by inducing antioxidant genes. Type 2 diabetes is an age-associated disease in which oxidative stress is involved, and moreover, some studies show that the prevalence is higher in men than in women, and therefore there are sex-associated differences. Thus, the aim of this study was to evaluate the role of estrogens in protecting against oxidative stress in type 2 diabetic males and females. For this purpose, we used Goto-Kakizaki rats, which develop type 2 diabetes with age. We found that female diabetic ra…

Infiltrating mast cell-mediated stimulation of estrogen receptor activity in breast cancer cells promotes the luminal phenotype

2019

Abstract Tumor growth and development is determined by both cancer cell–autonomous and microenvironmental mechanisms, including the contribution of infiltrating immune cells. Because the role of mast cells (MC) in this process is poorly characterized and even controversial, we investigated their part in breast cancer. Crossing C57BL/6 MMTV-PyMT mice, which spontaneously develop mammary carcinomas, with MC-deficient C57BL/6-KitW-sh/W-sh (Wsh) mice, showed that MCs promote tumor growth and prevent the development of basal CK5-positive areas in favor of a luminal gene program. When cocultured with breast cancer cells in vitro, MCs hindered activation of cMET, a master regulator of the basal pr…

Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: A compa…

2017

As the knowledge on the estrogenic system in the brain grows, the possibilities to modulate it in order to afford further neuroprotection in brain damaging disorders so do it. We have previously demonstrated the ability of the selective estrogen receptor modulator, bazedoxifene (BZA), to reduce experimental ischemic brain damage. The present study has been designed to gain insight into the molecular mechanisms involved in such a neuroprotective action by investigating: 1) stroke-induced apoptotic cell death; 2) expression of estrogen receptors (ER) ERα, ERβ and the G-protein coupled estrogen receptor (GPER); and 3) modulation of MAPK/ ERK1/2 and PI3K/Akt signaling pathways. For comparison, …

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

2019

Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At…

Interspecies differences in cancer susceptibility and toxicity.

1999

One of the most complex challenges to the toxicologist represents extrapolation from laboratory animals to humans. In this article, we review interspecies differences in metabolism and toxicity of heterocyclic amines, aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related compounds, endocrine disrupters, polycyclic aromatic hydrocarbons, tamoxifen, and digitoxin. As far as possible, extrapolations to human toxicity and carcinogenicity are performed. Humans may be more susceptible to the carcinogenic effect of heterocyclic amines than monkeys, rats, and mice. Especially, individuals with high CYP1A2 and 3A4 activities and the rapid acetylator phenotype may be expected to have …

Direct antioxidant and protective effect of estradiol on isolated mitochondria

2009

AbstractEstrogens have antioxidant properties which are due to their ability to bind to estrogen receptors and to up-regulate the expression of antioxidant enzymes via intracellular signalling pathways. Mitochondria are key organelles in the development of age-associated cellular damage. Recently, estrogen receptors were identified in mitochondria. The aim of this paper was to test whether estradiol directly affects mitochondria by preventing oxidative stress and protecting frail mitochondria. Incubation with estradiol at normal intracellular concentrations prevents the formation of reactive oxygen species by mitochondria in a saturable manner. Moreover, estradiol protects mitochondrial int…