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Receptor Alpha (receptor + alpha)
Kinds of Receptor Alpha Selected AbstractsIslet-1 Expression and its Colocalisation with Luteinising Hormone, Thyroid-Stimulating Hormone and Oestrogen Receptor Alpha in the Developing Pituitary Gland of the Sheep FoetusJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2005J. Liu Abstract Islet-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Oestrogen receptor (ER) and its expression may be involved in regulating pituitary development and its hormone-secreting function. Islet-1 expression and its correlations to ER in the developing pituitary gland are unknown. We therefore determined the pituitary cell specific expression of Islet-1 and its colocalisation with ER alpha (ER,) in sheep foetus by immunohistochemistry. The results demonstrated that Islet-1-immunoreacitive (ir) cells were distributed throughout the pituitary gland from day 60 of gestation until birth. The Islet-1-ir cell number was significant higher at day 90 and 120 of gestation compared to that at day 60 and at birth. All of the ER,-ir cells were colocalised with Islet-1 at day 60 of gestation, although a few ER,-ir cells were negative for Islet-1 in the later stage of gestation. The dominant cell type expressing Islet-1 is the gonadotroph, although small proportions of thyrotrophs and lactotrophs also express Islet-1. The proportion of luteinising hormone-ir gonadotrophs possessing Islet-1 kept rising from day 60 to day 120 of gestation and persisted until birth. The proportion of thyroid-stimulating hormone-ir cells expressing Islet-1 was at a high level from day 60,120 of the gestation and significantly declined at birth. The percentage of prolactin (PRL)-ir cells expressing Islet-1 was about 20% at day 60 of gestation. Very few PRL-ir cells contained Islet-1 in later stages of gestation. These data suggest that the development and functional establishment of pituitary gonadotrophs, thyrotrophs and lactotrophs might be regulated by the expressions of Islet-1 and ER, and by their interactions, although any mechanisms need to be elucidated further. [source] Immunohistochemical Studies on Oestrogen Receptor Alpha (ER,) and the Proliferative Marker Ki-67 in the Sow Uterus at Different Stages of the Oestrous CycleREPRODUCTION IN DOMESTIC ANIMALS, Issue 1 2003S Sukjumlong Contents In order to better understand physiological changes during the different stages of the oestrous cycle, immunohistochemistry was used in the present study to investigate the distribution of oestrogen receptor alpha (ER,) as well as the proliferative marker Ki-67, in the sow uterus during the oestrous cycle. Uterine samples were collected from multiparous sows with normal reproductive performance at selected stages of the oestrous cycle: at late dioestrus (d 17), prooestrus (d 19), oestrous (d 1), early dioestrus (d 4) and dioestrus (d 11,12), respectively. The tissue samples were fixed in 10% formaldehyde, embedded in paraffin and subjected to immunohistochemistry using monoclonal antibodies against ER, (C-311) and Ki-67 (MM-1). In general, the immunostaining of both ER, and Ki-67 was confined to nuclei of the target cells. Variations were seen, not only at the different stages of the oestrous cycle, but also in the different tissue compartments of the uterus. In the epithelia, the strongest ER, staining and highest amount of positive Ki-67 cells were found at early dioestrus. In the myometrium, the highest levels of staining of both ER, and Ki-67 positive cells were found at pro-oestrus and oestrus. For the proliferative marker, Ki-67, no positive cells were found at dioestrus and late dioestrus in the epithelium and myometrium. In the connective tissue stroma (subepithelial layer), the highest number of ER, positive cells were found at oestrus, which was significantly different compared with other stages (p,0.05), whereas the levels of Ki-67 positive cells were relatively low and did not differ between the stages examined. Significant correlations between the number of ER, positive cells in the stroma and Ki-67 positive cells in the epithelia were observed. This suggests indirect regulatory mechanisms on epithelial proliferation via ER, in the stroma. In conclusion, these findings in the sow uterus show that the presence of ER, as well as Ki-67 protein varies not only between different stages of the oestrous cycle but also between different tissue compartments of the uterus. These findings indicate various regulatory mechanisms and stress the importance of localising ER, and proliferating cells in different uterine tissues. [source] ChemInform Abstract: Efficient Asymmetric Synthesis of (S)-2-Ethylphenylpropanoic Acid Derivative, a Selective Agonist for Human Peroxisome Proliferator-Activated Receptor Alpha.CHEMINFORM, Issue 49 2002Masahiro Nomura Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A nonsecosteroidal vitamin D receptor ligand with improved therapeutic window of bone efficacy over hypercalcemiaJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Masahiko Sato Abstract Vitamin D3 analogues were shown to be beneficial for osteoporosis and other indications, but their narrow therapeutic window between efficacy and hypercalcemia has limited their clinical utility. A nonsecosteroidal, tissue-selective, orally bioavailable, vitamin D receptor (VDR) ligand was ascertained to be efficacious in bone while having modest calcemic effects in vivo. This compound (VDRM2) potently induced Retinoid X Receptor alpha (RXR)-VDR heterodimerization (EC50,=,7.1,±,1.6,nM) and induced osteocalcin promoter activity (EC50,=,1.9,±,1.6,nM). VDRM2 was less potent in inducing Ca2+ channel transient receptor potential cation channel, subfamily V, member 6 (TRPV6) expression (EC50,=,37,±,12,nM). VDRM2 then was evaluated in osteopenic ovariectomized (OVX) rats and shown to dose-dependently restore vertebral bone mineral density (BMD) from OVX to sham levels at 0.08,µg/kg per day. Hypercalcemia was observed at a dose of 4.6,µg/kg per day of VDRM2, suggesting a safety margin of 57 [90% confidence interval (CI) 35,91]. 1,,25-dihydroxyvitamin D3 [1,,25(OH)2D], ED71, and alfacalcidol restored BMD at 0.030, 0.0055, and 0.046,µg/kg per day, respectively, whereas hypercalcemia was observed at 0.22, 0.027, and 0.23,µg/kg per day, indicating a safety margin of 7.3, 4.9, and 5.0, respectively (90% CIs 4.1,13, 3.2,7.7, and 3.5,6.7, respectively). Histomorphometry showed that VDRM2 increased cortical bone area and stimulated the periosteal bone-formation rate relative to OVX at doses below the hypercalcemic dose. By contrast, ED71 increased the periosteal bone-formation rate only above the hypercalcemic dose. VDRM2 suppressed eroded surface on trabecular bone surfaces at normal serum calcium dosage levels, suggesting dual anabolic and antiresorptive activity. In summary, vitamin D analogues were more potent than VDRM2, but VDRM2 had a greater safety margin, suggesting possible therapeutic potential. © 2010 American Society for Bone and Mineral Research [source] PDGFR-, signaling is critical for tooth cusp and palate morphogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2005Xun Xu Abstract Platelet-derived growth factor receptor alpha (PDGFR-,) and PDGF ligands are key regulators for embryonic development. Although Pdgfr, is spatially expressed in the cranial neural crest (CNC)-derived odontogenic mesenchyme, mice deficient for Pdgfr, are embryonic lethal, making it impossible to investigate the functional significance of PDGF signaling in regulating the fate of CNC cells during tooth morphogenesis. Taking advantage of the kidney capsule assay, we investigated the biological function of PDGF signaling in regulating tooth morphogenesis. Pdgfr, and Pdgfa are specifically and consistently expressed in the CNC-derived odontogenic mesenchyme and the dental epithelium, respectively, throughout all stages of tooth development, suggesting a paracrine function of PDGF signaling in regulating tooth morphogenesis. Highly concentrated expression patterns of Pdgfr, and Pdgfa are associated with the developing dental cusp, suggesting possible functional importance of PDGF signaling in regulating cusp formation. Loss of the Pdgfr, gene does not affect proper odontoblasts proliferation and differentiation in the CNC-derived odontogenic mesenchyme but perturbs the formation of extracellular matrix and the organization of odontoblast cells at the forming cusp area, resulting in dental cusp growth defect. Pdgfr,,/, mice have complete cleft palate. We show that the cleft palate in Pdgfr, mutant mice results from an extracellular matrix defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Collectively, our data suggests that PDGFR, and PDGFA are critical regulators for the continued epithelial,mesenchymal interaction during tooth and palate morphogenesis. Disruption of PDGFR, signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development. Developmental Dynamics 232:75,84, 2005. © 2004 Wiley-Liss, Inc. [source] Sex differences in progesterone receptor immunoreactivity in neonatal mouse brain depend on estrogen receptor , expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Christine K. Wagner Abstract Around the time of birth, male rats express higher levels of progesterone receptors in the medial preoptic nucleus (MPN) than female rats, suggesting that the MPN may be differentially sensitive to maternal hormones in developing males and females. Preliminary evidence suggests that this sex difference depends on the activation of estrogen receptors around birth. To test whether estrogen receptor alpha (ER,) is involved, we compared progesterone receptor immunoreactivity (PRir) in the brains of male and female neonatal mice that lacked a functional ER, gene or were wild type for the disrupted gene. We demonstrate that males express much higher levels of PRir in the MPN and the ventromedial nucleus of the neonatal mouse brain than females, and that PRir expression is dependent on the expression of ER, in these regions. In contrast, PRir levels in neocortex are not altered by ER, gene disruption. The results of this study suggest that the induction of PR via ER, may render specific regions of the developing male brain more sensitive to progesterone than the developing female brain, and may thereby underlie sexual differentiation of these regions. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 176,182, 2001 [source] Peroxisome proliferator-activated receptor alpha and the ketogenic dietEPILEPSIA, Issue 2008Tim Cullingford Summary Peroxisome proliferator-activated receptor alpha (PPAR,) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPAR, in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action. [source] Detection of the STAT5B,RARA fusion transcript in acute promyelocytic leukemia with the normal chromosome 17 on G-bandingEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Manabu Kusakabe Abstract Acute promyelocytic leukemia (APL) is characterized by chromosomal rearrangements of 17q21, leading to fusion of the gene-encoding retinoic acid receptor alpha (RARA) with a number of alternative partner genes. Signal transducer and activator of transcription 5 beta (STAT5B) is one of the alternative partners. We report a rare case of APL with STAT5B,RARA fusion transcript and the normal chromosome 17 on G-banding. Administration of all trans -retinoic acid improved disseminated intravascular coagulation without decrease of the leukemia cells in his peripheral blood and bone marrow. The molecular mechanism of fusion between STAT5B and RARA by chromosomal rearrangement is discussed based on the data from genome database. Clinical characteristics of APL with STAT5B,RARA are also discussed. [source] Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zoneGLIA, Issue 2 2009Alexandre I. Danilov Abstract Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFR,) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFR, were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFR, on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFR, among their progeny. © 2008 Wiley-Liss, Inc. [source] Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl,CoA dehydrogenase (MCAD),deficient mice,HEPATOLOGY, Issue 6 2008Hilde Herrema Medium-chain acyl,coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD,/, mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD,/, mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1, (Pgc-1,) and decreased peroxisome proliferator-activated receptor alpha (Ppar ,) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD,/, mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD,/, mice. During the APR, however, this flux was significantly decreased (,20%) in MCAD,/, mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD,/, mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD,/, mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD,/, mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.) [source] Low expression of the interleukin (IL)-4 receptor alpha chain and reduced signalling via the IL-4 receptor complex in human neonatal B cellsIMMUNOLOGY, Issue 1 2006Cuixia Tian Summary Diminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses. [source] Expression of estrogen receptor alpha increases leptin-induced STAT3 activity in breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Nadine A. Binai Abstract Adipositas correlates with an enhanced risk of developing malignant diseases such as breast cancer, endometrial tumor or prostate carcinoma, but the molecular basis for this is not well understood. Potential mechanisms include increased bioavailability of adipocytokines (e.g. leptin) and steroid hormones. Here, we investigated cross-talk between ER, (estrogen receptor alpha) and leptin-induced activation of signal transducer and activator of transcription 3 (STAT3), a transactivator of important oncogenes. Upon leptin binding to its receptor Ob-RL (obesity receptor), STAT3 tyrosine phosphorylation and transactivation activity were enhanced by simultaneously expressing ER,. Downregulation of ER, using small interfering RNA abolished leptin-induced STAT3 phosphorylation. Interestingly, leptin-mediated STAT3 activation was unaffected by co-stimulation with the ER, ligands estradiol (E2) or estrogen antagonists ICI182,780 and tamoxifen, implying that enhancement of leptin-mediated STAT3 activity is independent of ER, ligands. We also detected ER, binding to STAT3 and JAK2 (Janus kinase 2), resulting in enhanced JAK2 activity upstream of STAT3 in response to leptin that might lead to an increased ER,-dependent cell viability. Altogether, our results indicate that leptin-induced STAT3 activation acts as a key event in ER,-dependent development of malignant diseases. [source] To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGFJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2004Jörg Fiedler Abstract The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet-derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet-derived growth factor AA, -BB, and heterodimeric PDGF-AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF-AA, rhPDGF-BB, and rhPDGF-AB. The effect was highest in MPCs and for rhPDGF-BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP-2 as well as rxBMP-4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF-,1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF-AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone. © 2004 Wiley-Liss, Inc. [source] The Percentage of Pituitary Gonadotropes with Immunoreactive Oestradiol Receptors Increases in the Follicular Phase of the Ovine Oestrous CycleJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2001V. A. Tobin Abstract During the oestrous cycle, there is an alteration in gonadotrope responsiveness to gonadotropin releasing hormone (GnRH). One cellular mechanism that may be involved in these changes at the pituitary level is the hormonal regulation of oestrogen receptor (ER) expression. Using double-label immunohistochemistry, we examined the proportion of gonadotropes, lactotropes and somatotropes with immunoreactive (ir) oestrogen receptor alpha (ER,) in pituitary sections from ewes at three stages of the ovine oestrous cycle (n = 8 per group). The percentage of ER, positive cells that also stained positive for luteinizing hormone (LH) increased in the transition from the luteal phase to the follicular phase (n = 8), with no further increase at the time of oestrus (n = 8). In the pituitaries from the luteal phase sheep, only a small number (15%) of lactotropes and 4% of somatotropes were found to contain ir-ER, and there were no alterations across the oestrous cycle. When we examined pituitaries from ovariectomized (OVX) ewes treated (i.m.) with either oestradiol benzoate (50 µg) or oil vehicle for 2, 4, 6 or 16 h (n = 4 per group), there was no effect of treatment. In fact, the percentage of gonadotropes that were ER,-positive in OVX ewes was similar to that observed in the pituitaries from the follicular phase ewes, both of which display a high frequency of pulsatile GnRH secretion. We conclude that the number of gonadotropes that contain ir-ER, increases in the follicular phase of the oestrous cycle and this may enhance the responsiveness of these cells to oestrogen and GnRH. We suggest that this may be due to increased pulsatile GnRH input rather than rising oestrogen levels. [source] Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathwayJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2006Magdalena J. Polanczyk Abstract Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4+CD25+ regulatory T cells (Treg) but not a direct effect on effector T cells. In this report, we further investigated the effects of E2 on APC and Treg function. We found that E2 treatment in vivo strongly reduced recovery of APC from the peritoneal cavity and inhibited induction of the inflammatory cytokines interleukin (IL)-12 and interferon-, but enhanced secretion of IL-10. Moreover, E2-conditioned bone marrow-derived dendritic cells (BM-DC) could both enhance Treg activity and directly inhibit responder T cells in the absence of Treg cells. We examined whether this E2-induced inhibitory activity of BM-DC might involve costimulation through the recently described PD-1 pathway. Both E2 and pregnancy markedly enhanced PD-1 expression in several types of APC, including macrophages, B cells, and especially dendritic cells (DC). Similarly to E2-induced enhancement of FoxP3 expression and experimental autoimmune encephalomyelitis protection, E2-induced enhancement of PD-1+ cells was also mediated through estrogen receptor alpha (Esr1) in DC and macrophages but not in B cells. Based on antibody inhibition studies, PD-1 interaction with its ligands, PDL-1 and especially PDL-2, could mediate either positive or negative regulatory signaling in both mature and immature E2-conditioned DC, depending, respectively, on a relatively high (10:1) or low (1:1) ratio of T cells:BM-DC. These novel findings indicate that E2-induced immunomodulation is mediated in part through potentiation in BM-DC of the PD-1 costimulatory pathway. © 2006 Wiley-Liss, Inc. [source] A20 protects mice from lethal liver ischemia/reperfusion injury by increasing peroxisome proliferator-activated receptor-, expressionLIVER TRANSPLANTATION, Issue 11 2009Haley E. Ramsey The nuclear factor-,B inhibitory protein A20 demonstrates hepatoprotective abilities through combined antiapoptotic, anti-inflammatory, and pro-proliferative functions. Accordingly, overexpression of A20 in the liver protects mice from toxic hepatitis and lethal radical hepatectomy, whereas A20 knockout mice die prematurely from unfettered liver inflammation. The effect of A20 on oxidative liver damage, as seen in ischemia/reperfusion injury (IRI), is unknown. In this work, we evaluated the effects of A20 upon IRI using a mouse model of total hepatic ischemia. Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer. Although only 10%-25% of control mice injected with saline or the control rAd., galactosidase survived IRI, the survival rate reached 67% in mice treated with rAd.A20. This significant survival advantage in rAd.A20-treated mice was associated with improved liver function, pathology, and repair potential. A20-treated mice had significantly lower bilirubin and aminotransferase levels, decreased hemorrhagic necrosis and steatosis, and increased hepatocyte proliferation. A20 protected against liver IRI by increasing hepatic expression of peroxisome proliferator-activated receptor alpha (PPAR,), a regulator of lipid homeostasis and of oxidative damage. A20-mediated protection of hepatocytes from hypoxia/reoxygenation and H2O2 -mediated necrosis was reverted by pretreatment with the PPAR, inhibitor MK886. In conclusion, we demonstrate that PPAR, is a novel target for A20 in hepatocytes, underscoring its novel protective effect against oxidative necrosis. By combining hepatocyte protection from necrosis and promotion of proliferation, A20-based therapies are well-poised to protect livers from IRI, especially in the context of small-for-size and steatotic liver grafts. Liver Transpl 15:1613,1621, 2009. © 2009 AASLD. [source] Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjectsALLERGY, Issue 7 2009C. J. Corrigan Background:, Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7R,) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4+ T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Methods:, Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR+ DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Results:, Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR+ and CD11c+ cells infiltrated relatively late (24,48 h). The majority of TSLPR+ cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7R, chains. Maturation and stimulation with TSLP or polyriboinosinic,polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7R, chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells+ CD4+ T cells. Conclusion:, The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation. [source] A novel FIP1L1-PDGFRA mutant destabilizing the inactive conformation of the kinase domain in chronic eosinophilic leukemia/hypereosinophilic syndromeALLERGY, Issue 6 2009S. Salemi Background:, The Fip1-like-1,platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) gene fusion is a common cause of chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES), and patients suffering from this particular subgroup of CEL/HES respond to low-dose imatinib therapy. However, some patients may develop imatinib resistance because of an acquired T674I mutation, which is believed to prevent drug binding through steric hindrance. Methods:, In an imatinib resistant FIP1L1-PDGFRA positive patient, we analyzed the molecular structure of the fusion gene and analyzed the effect of several kinase inhibitors on FIP1L1-PDGFRA-mediated proliferative responses in vitro. Results:, Sequencing of the FIP1L1-PDGFRA fusion gene revealed the occurrence of a S601P mutation, which is located within the nucleotide binding loop. In agreement with the clinical observations, imatinib did not inhibit the proliferation of S601P mutant FIP1L1-PDGFRA-transduced Ba/F3 cells. Moreover, sorafenib, which has been described to inhibit T674I mutant FIP1L1-PDGFRA, failed to block S601P mutant FIP1L1-PDGFRA. Structural modeling revealed that the newly identified S601P mutated form of PDGFRA destabilizes the inactive conformation of the kinase domain that is necessary to bind imatinib as well as sorafenib. Conclusions:, We identified a novel mutation in FIP1L1-PDGFRA resulting in both imatinib and sorafenib resistance. The identification of novel drug-resistant FIP1L1-PDGFRA variants may help to develop the next generation of target-directed compounds for CEL/HES and other leukemias. [source] Aberrant distribution of junctional complex components in retinoic acid receptor alpha-deficient miceMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2010Sanny S.W. Chung Abstract Retinoic acid receptor alpha (RAR,)-deficient mice are sterile, with abnormalities in the progression of spermatogenesis and spermiogenesis. In this study, we investigated whether defective retinoid signaling involved at least in part, disrupted cell,cell interactions. Hypertonic fixation approaches revealed defects in the integrity of the Sertoli-cell barrier in the tubules of RAR,-deficient testes. Dye transfer experiments further revealed that coupling between cells from the basal to adluminal compartments was aberrant. There were also differences in the expression of several known retinoic acid (RA)-responsive genes encoding structural components of tight junctions and gap junctions. Immunostaining demonstrated a delay in the incorporation of zonula occludens (ZO-1), a peripheral component protein of tight junctions, into the Sertoli cell tight junctions. Markedly reduced expression of connexin-40 in mutant pachytene spermatocytes and round spermatids was found by in situ hybridization. An ectopic distribution of vimentin and disrupted cyclic expression of vimentin, which is usually tightly regulated during spermiogenesis, was found in RAR,-deficient testes at all ages examined. Thus, the specific defects in spermiogenesis in RAR,-deficient testes may correlate with a disrupted cyclic expression of RA-responsive structural components, including vimentin, a downregulation of connexin-40 in spermatogenic cells, and delayed assembly of ZO-1 into Sertoli cell tight junctions. Interestingly, bioinformatic analysis revealed that many genes that are components of tight junctions and gap junctions contained potential retinoic acid response element binding sites. Microsc. Res. Tech., 2010. © 2009 Wiley-Liss, Inc. [source] Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activationMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2010Rosa Sirianni Abstract The growth of many breast tumors is stimulated by estradiol (E2), which activates a classic mechanism of regulation of gene expression and signal transduction pathways inducing cell proliferation. Polyphenols of natural origin with chemical similarity to estrogen have been shown to interfere with tumor cell proliferation. The aim of this study was to investigate whether hydroxytyrosol (HT) and oleuropein (OL), two polyphenols contained in extra-virgin olive oil, can affect breast cancer cell proliferation interfering with E2-induced molecular mechanisms. Both HT and OL inhibited proliferation of MCF-7 breast cancer cells. Luciferase gene reporter experiments, using a construct containing estrogen responsive elements able to bind estrogen receptor alpha (ER,) and the study of the effects of HT or OL on ER, expression, demonstrated that HT and OL are not involved in ER,-mediated regulation of gene expression. However, further experiments pointed out that both OL and HT determined a clear inhibition of E2-dependent activation of extracellular regulated kinase1/2 belonging to the mitogen activating protein kinase family. Our study demonstrated that HT and OL can have a chemo-preventive role in breast cancer cell proliferation through the inhibition of estrogen-dependent rapid signals involved in uncontrolled tumor cell growth. [source] Immunohistochemical Studies on Oestrogen Receptor Alpha (ER,) and the Proliferative Marker Ki-67 in the Sow Uterus at Different Stages of the Oestrous CycleREPRODUCTION IN DOMESTIC ANIMALS, Issue 1 2003S Sukjumlong Contents In order to better understand physiological changes during the different stages of the oestrous cycle, immunohistochemistry was used in the present study to investigate the distribution of oestrogen receptor alpha (ER,) as well as the proliferative marker Ki-67, in the sow uterus during the oestrous cycle. Uterine samples were collected from multiparous sows with normal reproductive performance at selected stages of the oestrous cycle: at late dioestrus (d 17), prooestrus (d 19), oestrous (d 1), early dioestrus (d 4) and dioestrus (d 11,12), respectively. The tissue samples were fixed in 10% formaldehyde, embedded in paraffin and subjected to immunohistochemistry using monoclonal antibodies against ER, (C-311) and Ki-67 (MM-1). In general, the immunostaining of both ER, and Ki-67 was confined to nuclei of the target cells. Variations were seen, not only at the different stages of the oestrous cycle, but also in the different tissue compartments of the uterus. In the epithelia, the strongest ER, staining and highest amount of positive Ki-67 cells were found at early dioestrus. In the myometrium, the highest levels of staining of both ER, and Ki-67 positive cells were found at pro-oestrus and oestrus. For the proliferative marker, Ki-67, no positive cells were found at dioestrus and late dioestrus in the epithelium and myometrium. In the connective tissue stroma (subepithelial layer), the highest number of ER, positive cells were found at oestrus, which was significantly different compared with other stages (p,0.05), whereas the levels of Ki-67 positive cells were relatively low and did not differ between the stages examined. Significant correlations between the number of ER, positive cells in the stroma and Ki-67 positive cells in the epithelia were observed. This suggests indirect regulatory mechanisms on epithelial proliferation via ER, in the stroma. In conclusion, these findings in the sow uterus show that the presence of ER, as well as Ki-67 protein varies not only between different stages of the oestrous cycle but also between different tissue compartments of the uterus. These findings indicate various regulatory mechanisms and stress the importance of localising ER, and proliferating cells in different uterine tissues. [source] Distribution of sex steroid hormone receptors in the brain of an African cichlid fish, Astatotilapia burtoniTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 16 2010Lauren A. Munchrath Abstract Sex steroid hormones released from the gonads play an important role in mediating social behavior across all vertebrates. Many effects of these gonadal hormones are mediated by nuclear steroid hormone receptors, which are crucial for integration in the brain of external (e.g., social) signals with internal physiological cues to produce an appropriate behavioral output. The African cichlid fish Astatotilapia burtoni presents an attractive model system for the study of how internal cues and external social signals are integrated in the brain as males display robust plasticity in the form of two distinct, yet reversible, behavioral and physiological phenotypes depending on the social environment. In order to better understand where sex steroid hormones act to regulate social behavior in this species, we have determined the distribution of the androgen receptor, estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA and protein throughout the telencephalon and diencephalon and some mesencephalic structures of A. burtoni. All steroid hormone receptors were found in key brain regions known to modulate social behavior in other vertebrates including the proposed teleost homologs of the mammalian amygdalar complex, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area. Overall, there is high concordance of mRNA and protein labeling. Our results significantly extend our understanding of sex steroid pathways in the cichlid brain and support the important role of nuclear sex steroid hormone receptors in modulating social behaviors in teleosts and across vertebrates. J. Comp. Neurol. 518:3302,3326, 2010. © 2010 Wiley-Liss, Inc. [source] ESR1 amplification in endometrial carcinomas: hope or hyperbole?,THE JOURNAL OF PATHOLOGY, Issue 3 2008DSP Tan Abstract The ESR1 gene maps 6q25 and encodes for oestrogen receptor alpha, which has been shown to play a pivotal role in the development of breast and endometrial cancer. It has recently been reported that oestrogen receptor alpha expression may be driven in some cases by ESR1 gene amplification and that this phenomenon may be an early event in breast and endometrial carcinogenesis. Although copy number gains of 6q have been reported by several groups, their prevalence, association with oestrogen receptor alpha expression, and clinical implications have been a matter of controversy. Here we discuss the key issues regarding the methods employed in the identification of ESR1 amplification, and briefly review the current literature and recent controversies on the subject of ESR1 amplification in endometrial and breast cancers. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Control of Cell Number in the Bed Nucleus of the Stria Terminalis of Mice: Role of Testosterone Metabolites and Estrogen Receptor SubtypesTHE JOURNAL OF SEXUAL MEDICINE, Issue 4pt1 2010Shin-ichi Hisasue MD ABSTRACT Introduction., The bed nucleus of the stria terminalis (BNST) exhibits several sex differences that may be related to male sexual behavior and gender identity. In mice and rats, sex differences in the principal nucleus of the BNST (BNSTp) are due to sexually dimorphic cell death during perinatal life. Although testosterone treatment of newborn female rats increases BNSTp cell number, the relevant hormone metabolite(s) are not known, and the effect of testosterone on the development of BNSTp cell number in mice has not been examined. Aim., To identify the sex hormone metabolites and receptors controlling cell number, volume, and cell size in the BNSTp of mice. Methods., In the first experiment, C57BL/6J male mice were injected on the day of birth with peanut oil; females were injected with testosterone propionate (TP), estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), or oil alone, and the BNSTp of all animals was examined in adulthood. In the second experiment, to compare effects of EB to the effects of estrogen receptor subtype specific agonists, newborn female mice were injected with EB, propyl-pyrazole-triol (PPT, a selective estrogen receptor alpha [ER,] agonist), or diarylpropionitrile (DPN, a selective estrogen receptor beta [ER,] agonist). Main Outcome Measures., Nuclear volume measurements and stereological cell counts in the BNSTp in adulthood. Results., TP treatment of newborn females completely masculinized both BNSTp volume and cell number. EB masculinized neuron number, whereas DHTP had no effect on volume or cell number. In the second experiment, EB again fully masculinized neuron number in the BNSTp and in this study also masculinized BNSTp volume. PPT and DPN each significantly increased cell number, but neither completely mimicked the effects of EB. Conclusions., We conclude that estrogenic metabolites of testosterone control sexually dimorphic cell survival in the BNSTp and that activation of both ER, and ER, may be required for complete masculinization of this brain region. Hisasue S, Seney ML, Immerman E, and Forger NG. Control of cell number in the bed nucleus of the stria terminalis of mice: Role of testosterone metabolites and estrogen receptor subtypes. J Sex Med 2010;7:1401,1409. [source] Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissueTHE PROSTATE, Issue 8 2009Thomas J. Walton Abstract BACKGROUND Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ER,) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. METHODS Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ER,), estrogen receptor alpha (ER,), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann,Whitney U -test. Correlation coefficients were analyzed using Spearman's test. RESULTS Significant positive correlations were seen when AR and AR-dependent PSA, and ER, and ER,-dependent PGR were compared, indicating a representative population of RNA transcripts. ER, gene expression was significantly over-expressed in the cancer group compared with benign controls (P,<,0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P,<,0.05). There were no significant differences in AR, ER, or PSA expression between the groups. This study represents the first to show an upregulation of ER, gene expression in laser microdissected prostate cancer specimens. CONCLUSIONS In concert with recent studies the findings suggest differential production of ER, splice variants, which may play important roles in the genesis of prostate cancer. Prostate 69: 810,819, 2009. © 2009 Wiley-Liss, Inc. [source] Liver gene expression in relation to hepatic steatosis and lipid secretion in two duck speciesANIMAL GENETICS, Issue 1 2010F. Hérault Summary The susceptibility to development of hepatic steatosis is known to differ between Muscovy and Pekin ducks. Although some experiments were conducted to decipher these differences, few data have been produced to analyse the role of specific genes in this process. For this purpose, expression levels of genes involved in lipid (ATP citrate lyase, malic enzyme 1, fatty acid synthase, stearoyl-CoA desaturase 1, diacylglycerol O-acyl transferase 2, microsomal triglyceride transfer protein, apolipoprotein A1, apolipoprotein B, sterol regulatory element binding factor 1, hepatocyte nuclear factor 4, choline/ethanolamine phosphotransferase 1, carnitine palmitoyl transferase 1A, peroxisome proliferator-activated receptor alpha and sterol O-acyltransferase) and carbohydrate (activating transcription factor 4 or cAMP-response element binding protein, mitochondrial malate dehydrogenase 2 and carbohydrate responsive element binding protein) metabolism and in other functions were analysed in the liver of Pekin and Muscovy ducks fed ad libitum or overfed. A specific positive effect of feeding was observed on the expression of genes involved mainly in fatty acids and TG synthesis and glycolysis, and negative effect on genes involved in ,-oxidation. Interestingly, a strong species effect was also observed on stearoyl-CoA desaturase 1 and to a lesser extent on diacylglycerol O-acyl transferase 2 expression, leading to large differences in expression levels between Pekin and Muscovy overfed ducks, which could explain the difference in lipid metabolism and steatosis ability observed between the two duck species. These results should shed light on gene expression that might underlie susceptibility to hepatic steatosis in humans. [source] Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseasesBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Katerina E. Panteli Summary A number of growth factors are involved in clonal haematopoietic expansion and their clinical significance in patients with chronic myeloproliferative diseases requires further evaluation. Using enzyme-linked immunosorbent assays, we analysed serum levels of interleukin (IL)-1a, IL-1b, IL-2, IL-6, the soluble IL-2 receptor alpha (sIL-2Ra), and thrombopoietin (TPO), in 25 individuals with myelofibrosis with myeloid metaplasia (MMM), 40 with essential thrombocythaemia (ET), eight with polycythaemia vera (PV), 10 patients with chronic myeloid leukaemia (CML) and 27 normal controls. These were correlated with clinicopathological characteristics including overall survival, and histopathological bone marrow features, including angiogenesis. The serum derived from patients with MMM, ET, PV and CML contained significantly higher IL-2 and sIL-2Ra than healthy subjects, while IL-6 levels were higher only in MMM and CML than controls. IL-2, sIL-2Ra and IL-6 levels were raised during the transformation phase of CML, during progression of MMM to AML, and ET and PV to myelofibrosis (P < 0·001). There was a positive correlation between IL-2, sIL-2Ra, IL-6 and angiogenesis in bone marrow samples. Cytokines may be useful markers for predicting clinical evolution, reflecting increased angiogenesis. This requires further evaluation to guide diagnostic and therapeutic options. [source] Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol- O -methyltransferase are associated with familial prostate carcinoma risk in a Japanese populationCANCER, Issue 7 2003Kazuhiro Suzuki M.D. Abstract BACKGROUND Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen-related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS In the current study, 101 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 114 healthy age and residence-matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol- O -methyltransferase (COMT) genes were analyzed. RESULTS For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97,5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02,3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85,2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high-grade carcinoma (OR, 2.59; 95% CI, 1.47,4.46; P = 0.048). The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72,5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61,10.99; P = 0.002). CONCLUSIONS Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11639 [source] Triptolide abrogates oncogene FIP1L1-PDGFR, addiction and induces apoptosis in hypereosinophilic syndromeCANCER SCIENCE, Issue 11 2009Yanli Jin The pathogenesis of hypereosinophilic syndrome (HES) in some patients is highly dependent on FIP1-Like-1 (FIP1L1),platelet-derived growth factor receptor alpha (PDGFR,), which can generate sustained activation signaling to maintain a cell malignant phenotype. HES usually shows good response to the tyrosine kinase inhibitor imatinib, but mutations in FIP1L1-PDGFR, (e.g. T674I) can confer acquired resistance to imatinib. An alternative therapeutic strategy other than with tyrosine kinase inhibitors is needed to overcome acquired drug resistance. We hypothesized that switching off the crucial chimeric oncoprotein FIP1L1-PDGFR, on which HES cells depend, should have deleterious effects on the cancer cells. We used low concentrations of triptolide, a transcription inhibitor, to shut down the expression of FIP1L1-PDGFR,. EOL-1 cells and BaF3 cells expressing wild-type or T674I FIP1L1-PDGFR, were treated with triptolide, and signaling pathways, cell cycling, and apoptosis were analyzed by RT-PCR, immunoblotting, and flow cytometry, respectively. The results revealed that at nanomolar concentrations triptolide decreased the levels of mRNA and protein of FIP1L1-PDGFR, and the growth of the neoplastic cells, regardless of the mutational status of PDGFR,. Triptolide also downregulated the signaling molecules Stat3, Akt, and Erk1/2, which are downstream from PDGFR,, and induced G1 cell-cycle arrest. Triptolide time- and dose-dependently induced apoptosis by decreasing the anti-apoptotic proteins Mcl-1 and Bcl-XL,triggering the intrinsic apoptotic pathway. In conclusion, triptolide has potent activity against malignant cells in HES bearing FIP1L1-PDGFR,, regardless of its mutational status that confer acquired resistance to imatinib. Our results suggest that triptolide may be a promising agent in the treatment of HES. (Cancer Sci 2009; 00: 000,000) [source] Distributions of estrogen receptors alpha and beta in sympathetic neurons of female rats: Enriched expression by uterine innervationDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2002Elena V. Zoubina Abstract Estrogen modulates many features of the sympathetic nervous system, including cell numbers and ganglion synapses, and can induce uterine sympathetic nerve degeneration. However, distributions of estrogen receptors , and , within sympathetic neurons have not been described, and their regulation by target tissue or estrogen levels has not been explored. We used immunofluorescence and retrograde tracing to define estrogen receptor expression in sympathetic neurons at large in pre- and paravertebral ganglia and in those projecting to the uterine horns. Estrogen receptor , immunoreactivity was present in 29 ± 1%, while estrogen receptor , was expressed by 92 ± 1% of sympathetic neurons at large. The proportions of neurons expressing these receptors were comparable in the superior cervical and thoraco-lumbar paravertebral ganglia from T11 through L5, and in the suprarenal, celiac, and superior mesenteric prevertebral ganglia. Injections of FluoroGold into the uterine horns resulted in labeled neurons, with peak occurrences in T13, L1, and the suprarenal ganglion. Uterine-projecting neurons showed small but significantly greater incidence of estrogen receptor , expression relative to the neuronal population at large, whereas the proportion of uterine-projecting neurons with estrogen receptor ,-immunoreactivity was nearly threefold greater. Numbers of estrogen receptor-expressing neurons were not altered by acute estrogen administration. We conclude that the vast majority of sympathetic neurons express estrogen receptor , immunoreactive protein, whereas a smaller, presumably overlapping subset expresses the estrogen receptor ,. Expression of the latter apparently can be enhanced by target-mediated mechanisms. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 14,23, 2002 [source] | ||||||||||||||||||||||||||||