scholarly journals Immunolocalization of Estrogen Receptor β in the Mouse Brain: Comparison with Estrogen Receptor α

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2055-2067 ◽  
Author(s):  
Sudha Warrier Mitra ◽  
Elena Hoskin ◽  
Joel Yudkovitz ◽  
Lisset Pear ◽  
Hilary A. Wilkinson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cerebral Cortex ◽  
Olfactory Bulb ◽  
Mouse Brain ◽  
Preoptic Area ◽  
Estrogen Receptor Α ◽  
Hypothalamic Nucleus ◽  
Similar Distribution ◽  
Dependent Manner ◽  
The Brain

Estrogen receptor α (ERα) and ERβ are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ERβ-selective antibody that cross-reacts with mouse, rat, and human ERβ protein and its use to determine the distribution of ERβ in the murine brain. Further, a previously characterized polyclonal antibody to ERα was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ERβ immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ERα-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ERβ and ERα in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.

scholarly journals Sex Differences in Epigenetic Regulation of the Estrogen Receptor-α Promoter within the Developing Preoptic Area

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2297-2305 ◽  
Author(s):  
Joseph R. Kurian ◽  
Kristin M. Olesen ◽  
Anthony P. Auger
Keyword(s):  
Dna Methylation ◽  
Estrogen Receptor ◽  
Sex Differences ◽  
Preoptic Area ◽  
Estrogen Receptor Α ◽  
Sexually Dimorphic ◽  
Brain And Behavior ◽  
Maternal Interaction ◽  
Methylation Patterns ◽  
The Brain

Sex differences in the brain are largely organized by a testicular hormone surge that occurs in males shortly after birth. Although this hormone surge is transient, sex differences in brain and behavior are lasting. Here we describe a sex difference in DNA methylation of the estrogen receptor-α (ERα) promoter region within the developing rat preoptic area, with males exhibiting more DNA methylation within the ERα promoter than females. More importantly, we report that simulating maternal grooming, a form of maternal interaction that is sexually dimorphic with males experiencing more than females during the neonatal period, effectively masculinizes female ERα promoter methylation and gene expression. This suggests natural variations in maternal care that are directed differentially at males vs. females can influence sex differences in the brain by creating sexually dimorphic DNA methylation patterns. We also find that the early estradiol exposure may contribute to sex differences in DNA methylation patterns. This suggests that early social interaction and estradiol exposure may converge at the genome to organize lasting sex differences in the brain via epigenetic differentiation.

scholarly journals Estrogen Receptor α Gene Promoter 0/B Usage in the Rat Sexually Dimorphic Nucleus of the Preoptic Area

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1923-1928 ◽  
Author(s):  
Tomohiro Hamada ◽  
Yasuo Sakuma
Keyword(s):  
Estrogen Receptor ◽  
Sexual Differentiation ◽  
Preoptic Area ◽  
Gene Promoter ◽  
Estrogen Receptor Α ◽  
Egfp Expression ◽  
Sexually Dimorphic ◽  
Transgenic Rats ◽  
The Core ◽  
Sexually Dimorphic Nucleus

The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is two to four times larger in male rats than in females; however, the mechanism for the establishment of sexual dimorphism and the function of this nucleus is almost unknown. Perinatal estrogen can cause sexual dimorphism via the estrogen receptor α (ERα). Recently, transgenic rats were generated that express enhanced green fluorescent protein (EGFP) under the control of the ERα gene promoter 0/B to tag ERα-positive neurons in the brain. In the present study, we examined whether this EGFP expression could be a marker for the SDN-POA in adults. EGFP-labeled cells were distributed in the core of the SDN-POA (0/B-SDN) of male and female transgenic rats, in accordance with the Nissl staining and immunoreactivity for the SDN marker, calbindin. They were also immunoreactive for ERα. The core was bigger in volume and contained more 0/B-SDN neurons in males than in females. The EGFP-tagged cells were packed more densely in the female core than that in males. Subcutaneous injection of 100 μg 17β-estradiol to females on the day of birth, or orchidectomy of male neonates, reversed the sexually dimorphic phenotype of the volume of the 0/B-SDN, despite not affecting the cell number. We suggest that this EGFP expression in the SDN-POA could be a useful marker to clarify the sexual differentiation and function of the SDN-POA. Moreover, the ERα gene promoter 0/B plays a key role in the organization of the sexual differentiation of the SDN-POA.

scholarly journals Membrane Estrogen Receptor-Dependent Extracellular Signal-Regulated Kinase Pathway Mediates Acute Activation of Endothelial Nitric Oxide Synthase by Estrogen in Uterine Artery Endothelial Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Dong-bao Chen ◽  
Ian M. Bird ◽  
Jing Zheng ◽  
Ronald R. Magness
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Uterine Artery ◽  
Fluorescein Isothiocyanate ◽  
Estrogen Receptor Α ◽  
Dependent Manner ◽  
Enos Phosphorylation

Abstract Rapid uterine vasodilatation after estrogen administration is believed to be mediated by endothelial production of nitric oxide (NO) via endothelial NO synthase (eNOS). However, the mechanism(s) by which estrogen activates eNOS in uterine artery endothelial cells (UAEC) is unknown. In this study, we observed that estradiol-17β (E2) and E2-BSA rapidly (<2 min) increased total NOx production in UAEC in vitro. This was associated with rapid eNOS phosphorylation and activation but was unaltered by pretreatment with actinomycin-D. estrogen receptor-α protein was detectable in isolated plasma membrane proteins by immunoblotting, and E2-BSA-fluorescein isothiocyanate binding was evident on the plasma membrane of UAEC. E2 did not mobilize intracellular Ca2+, but E2 and ionomycin in combination induced greater eNOS phosphorylation than either E2 or ionomycin alone. E2 did not stimulate rapid Akt phosphorylation. E2 stimulated rapid ERK2/1 activation in a time- and dose-dependent manner, with maximal responses observed at 5–10 min with E2 (10 nm to 1 μm) treatment. Acute activation of eNOS and NOx production by E2 could be inhibited by PD98059 but not by LY294002. When E2-BSA was applied, similar responses in NOx production, eNOS, and ERK2/1 activation to those of E2 were achieved. In addition, E2 and E2-BSA-induced ERK2/1 activation and ICI 182,780 could inhibit NOx production by E2. Thus, acute activation of eNOS to produce NO in UAEC by estrogen is at least partially through an ERK pathway, possibly via estrogen receptor localized on the plasma membrane. This pathway may provide a novel mechanism for NO-mediated rapid uterine vasodilatation by estrogen.

scholarly journals The Ability of Estradiol to Induce Fos Expression in a Subset of Estrogen Receptor-α-Containing Neurons in the Preoptic Area of the Ewe Depends on Reproductive Status1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Ivan Stefanovic ◽  
Brian Adrian ◽  
Heiko T. Jansen ◽  
Michael N. Lehman ◽  
Robert L. Goodman
Keyword(s):  
Estrogen Receptor ◽  
Preoptic Area ◽  
Estrogen Receptor Α ◽  
Fos Expression

scholarly journals Estrogen Induces Repression of the Breast Cancer and Salivary Gland Expression Gene in an Estrogen Receptor α–Dependent Manner

2008 ◽  
Vol 68 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Nancy Bretschneider ◽  
Heike Brand ◽  
Nicola Miller ◽  
Aoife J. Lowery ◽  
Michael J. Kerin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Salivary Gland ◽  
Estrogen Receptor Α ◽  
Dependent Manner

scholarly journals Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

2005 ◽  
Vol 16 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Filippo Acconcia ◽  
Paolo Ascenzi ◽  
Alessio Bocedi ◽  
Enzo Spisni ◽  
Vittorio Tomasi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Estrogen Receptor Α ◽  
Membrane Localization ◽  
Target Cells ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

scholarly journals Estrogen receptor α phosphorylated at Ser216 confers inflammatory function to mouse microglia

2019 ◽  
Author(s):  
Sawako Shindo ◽  
Shih-Heng Chen ◽  
Saki Gotoh ◽  
Kosuke Yokobori ◽  
Hao Hu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inflammatory Cytokines ◽  
Estrogen Receptor Α ◽  
Microglia Activation ◽  
Immune Functions ◽  
Protein Levels ◽  
Brain Extracts ◽  
Anti Inflammatory ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Abstract Background Estrogen has been suggested to regulate anti-inflammatory signaling in brain microglia through estrogen receptor α (ERα), the only resident immune cells of the brain. The mechanism of how ERα regulates is not well understood. Previously, ERα is phosphorylated at Ser216 in mouse neutrophils, regulating their infiltration into the uterus. Therefore, ERα has now been examined as to its phosphorylation in microglia to regulate their inflammatory functions.MethodsAn antibody against an anti-phospho-S216 peptide of ERα (αP-S216) was used for double immunofluorescence staining to detect to ERα in cultured microglia. A knock-in (KI) mouse line bearing the phosphorylation-blocked ERα mutation S216A (ERα KI) was generated to examine whether this phosphorylation regulate immune functions of microglia.ResultsPhosphorylated ERα at Ser216 was present in microglia but not astrocytes. Staining with an anti-Iba-1 antibody showed that microglia activation was augmented in substantial nigra of ERα KI brains. Lipopolysaccharide (LPS) treatments aggravated microglia activation in ERα KI brains, pro-inflammatory cytokines were increased while anti-inflammatory cytokines were decreased at mRNA and protein levels in whole brain extracts. These increases and decreases of cytokine proteins were also observed in LPS-treated microglia cultured from brains of ERα KI neonates. FACS analysis revealed that ERα KI mutation increased number of IL-6 producing microglia and apoptosis. ERα KI mice decreased motor connection ability in Rotarod tests.ConclusionsBlocking of Ser216 phosphorylation aggravated microglia activation and inflammation of mouse brain, thus confirming that phosphorylated ERα exerts anti-inflammatory functions. ERα KI mice enable us to further investigate the mechanism by which phosphorylated ERα regulates brain immunity and inflammation.

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