Two distinct isoforms of the human progesterone receptor (hPR-A and hPR-B) have been identified previously. They differ only in that hPR-B contains an additional 164 amino acids at terminus. Among various species these two forms arise as a result either alternate initiation translation from same mRNA or by transcription promoters within gene. In order to understand reason for their existence, we studied transcriptional capacity individual receptors observed activity was influenced strongly...

Sex has a role in the incidence and outcome of neurological illnesses, also influencing response to treatments. Neuroinflammation is involved onset progression several diseases, fact that estrogens have anti-inflammatory activity suggests these hormones may be determinant sex-dependent manifestation brain pathologies. We describe significant differences transcriptome adult male female microglia, possibly originating from perinatal exposure sex steroids. Microglia isolated brains maintain...

After neuronal injury and in several neurodegenerative diseases, activated microglia secrete proinflammatory molecules that can contribute to the progressive neural damage. The recent demonstration of a protective role estrogen disorders humans experimental animal models led us investigate whether this hormone regulates inflammatory response CNS. We here show exerts an anti-inflammatory activity on primary cultures rat microglia, as suggested by blockage phenotypic conversion associated with...

Estrogen is an immunoregulatory agent, in that hormone deprivation increases while 17beta-estradiol (E2) administration blocks the inflammatory response; however, underlying mechanism still unknown. The transcription factor p65/relA, a member of nuclear kappaB (NF-kappaB) family, plays major role inflammation and drives expression proinflammatory mediators. Here we report novel action E2 inflammation. We observe macrophages lipopolysaccharide-induced DNA binding transcriptional activity p65...

Abstract Although 17β-estradiol (E 2 ) anti-inflammatory activity has been well described, very little is known about the effects of this hormone on resolution phase inflammatory process. Here, we identified a previously unreported ERα-mediated effect E machinery. The study showed that activation intracellular estrogen receptor shortens LPS-induced pro-inflammatory and, by influencing intrinsic and extrinsic programs, triggers inflammation in RAW 264.7 cells. Through regulation SOCS3 STAT3...

Beyond the key role in reproductive and cognitive functions, estrogens have been shown to protect against neurodegeneration associated with acute chronic injuries of adult brain. Current hypotheses reconcile this activity a direct effect 17β-estradiol (E 2 ) on neurons. Here we demonstrate that brain macrophages are also involved E action Systemic administration hormone prevents, time- dose-dependent manner, activation microglia recruitment peripheral monocytes induced by intraventricular...

It has been previously demonstrated that 17beta-estradiol (E(2)) inhibits the response of microglia, resident brain macrophages, to acute injuries in specific regions. We here show effect E(2) inflammation is widespread and hormone reduces expression inflammatory mediators, such as monocyte chemoattractant protein-1, macrophage protein-2, TNF-alpha, induced by lipopolysaccharide, demonstrating microglia are a direct target estrogen action brain. Using APP23 mice, an animal model Alzheimer's...

During their reproductive years, women are generally protected from cardiovascular disease events by estrogen-replete status. Our starting hypothesis was that lower estrogen levels after menopause associated with macrophage activation profiles skewed toward proinflammatory phenotypes. Research Design and Setting: This an in vitro ex vivo study human blood-derived macrophages.We obtained blood 12 healthy male donors for the 5 premenopausal 8 postmenopausal study.We measured immunophenotypes...

In addition to their well known control of reproductive functions, estrogens modulate important physiological processes. The identification compounds with tissue-selective activity will lead new drugs mimicking the beneficial effects estrogen on prevention osteoporosis and cardiovascular or neurodegenerative diseases, while avoiding its detrimental proliferative effects. As an innovative model for in vivo selective receptor modulators (SERMs), we engineered a mouse genome express luciferase...

The neuroblastoma cell line SK-ER3, which is stably transfected with the estrogen receptor (ER), was used to study effect of insulin and insulin-like growth factors (IGF-I IGF-II) on morphological differentiation induced by estrogens. data demonstrate that related control expressing ER, but not parental line. Effects elicited in SK-ER3 cells can be blocked ER antagonists. Transient transfection studies further confirm an IGFs modulation ER-activated promoters. results presented support...

Although several lines of evidence have indicated that menopause is associated with increased susceptibility to neurological disorders, the mechanisms involved in this phenomenon remain be elucidated. Because neuroinflammation a common feature number brain diseases, we hypothesized cessation ovarian functions and consequent decrease estrogen receptor (ER)-mediated antiinflammatory activity may represent trigger for postmenopausal dysfunctions. The aim present study was investigate effects...

Acquisition of the M1 or M2 phenotypes by microglia has been shown to occur during development pathological conditions, with activation being widely involved in neurotoxicity relation anatomical localization and reactivity subtypes cells. On contrary, little is known on ability undergo polarization interleukin-4 (IL4), typical M2a signal for peripheral macrophages. Recombinant mouse IL4 was injected third cerebral ventricle mice induce brain alternative polarization. The mRNA levels Fizz1,...

Abstract Beyond the physiology of reproduction, estrogen controls homeostasis several tissues. Although macrophages play a key role in tissue remodeling, interplay with is still ill defined. Using transcriptomic approach we first obtained comprehensive list genes that are differentially expressed peritoneal response to physiological levels 17β-estradiol (E 2 ) injected intact female mice. Our data also showed dynamic nature macrophage E and pointed specific biological programs induced by...

Epidemiological data suggest a sexual dimorphism in Parkinson disease (PD), with women showing lower risk of developing PD. Vulnerability the nigrostriatal pathway may be influenced by exposure to estrogenic stimulation throughout fertile life. To further address this issue, we analyzed progression damage, microglia and astrocyte activation polarization triggered intrastriatal injection dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) male, female ovariectomized (OVX) mice, as well OVX...

Induction of apoptosis mononucleated cells is a physiological process for regulating the intensity immune response. The female steroid hormones estrogen (E2) and progesterone (Prog) are known to modulate reactivity system; recently it has been demonstrated that they can regulate induction endothelial osteoblasts. TNF-α-mediated well characterized in myeloid cells. We investigated whether E2 Prog could interfere with TNF-α-induced monoblastoid U937 cell line. Treatment or increased survival...

This report describes the identification of a negative regulator estrogen and progesterone receptor function. Using reconstituted estrogen-responsive transcription system in Saccharomyces cerevisiae, we have identified "repressor function," which when mutated, increases transcriptional activity receptors. In case this mutation sensitivity estrogen-mediated activation by at least four orders magnitude. Analysis derivatives indicated that repressor specifically affects TAF1 domain receptor....