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Details for receptor: ER-alpha

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EndoNet ID: ENR00704

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Synonyms

  • estrogen receptor 1
  • ER-alpha
  • estrogen receptor alpha
  • estradiol receptor
  • ERalpha
  • ESR1

General information

  • ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. [1]
  • Detected in Hippocampus [1]
  • ER-alpha was restricted to the cell nuclei of epithelial cells of the mammary gland. [2]
  • ER-alpha in the normal mammary tissue varies with the degree of lobular development, in parallel with cell proliferation. [3]
  • ER alpha mRNA expression levels in osteoblasts increased only slightly until day 10 (2.3+/-1.7 fold) and then remained constant. [4]
  • Uterus, mammary gland, placenta, liver, central nervous system (CNS), cardiovascular system, bone have a high ER-alpha content. [5]
  • In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells. [1]
  • ER-alpha and ER-beta are functionally expressed in the prostate gland. [6]
  • ER-alpha mRNA was detected in MCF7, mammary gland, endometrium, ovary, lung, kidney,liver and adrenal gland samples. [7]
  • ER-alpha was detected in eccrine sweat glands, sebaceous glands, epidermis and outer root sheath of hair follicles. [8]
  • Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha. [9]
  • The AR, ER-alpha and ER-beta are expressed in the growth plate and the osteoblasts. [10]
  • ER-alpha is the dominant receptor in the adult uterus, it is expressed when the tissue matures. [11]
  • Purified normal human osteoclasts expressed ER-alpha mRNA. Treatment of the cells with 17-beta estradiol suppressed IL-1R1 mRNA, but increased IL-1R2 message levels. [12]
  • It is estimated that only 7-10% of the epithelial cells in the normal human breast express ER-alpha, and it has been shown that this expression fluctuates with the menstrual cycle. [13]
  • GnRH neurons (GT1-7) express receptors for estrogen [estrogen receptor-alpha and-13(ERa and ERI3)]. [14]
  • Differential expression of estrogen receptor-beta (ER beta) in human pituitary tumors: functional interactions with ER alpha and a tumor-specific splice variant. [15]

Links to other resources

UniProt P03372
Ensembl ENST00000456483

Subunit information

long isoform (1 times)

Sequence 
MTMTLHTKA SGMALLHQI QGNELEPLN 
RPQLKIPLE RPLGEVYLD SSKPAVYNY 
PEGAAYEFN AAAAANAQV YGQTGLPYG 
PGSEAAAFG SNGLGGFPP LNSVSPSPL 
MLLHPPPQL SPFLQPHGQ QVPYYLENE 
PSGYTVREA GPPAFYRPN SDNRRQGGR 
ERLASTNDK GSMAMESAK ETRYCAVCN 
DYASGYHYG VWSCEGCKA FFKRSIQGH 
NDYMCPATN QCTIDKNRR KSCQACRLR 
KCYEVGMMK GGIRKDRRG GRMLKHKRQ 
RDDGEGRGE VGSAGDMRA ANLWPSPLM 
IKRSKKNSL ALSLTADQM VSALLDAEP 
PILYSEYDP TRPFSEASM MGLLTNLAD 
RELVHMINW AKRVPGFVD LTLHDQVHL 
LECAWLEIL MIGLVWRSM EHPGKLLFA 
PNLLLDRNQ GKCVEGMVE IFDMLLATS 
SRFRMMNLQ GEEFVCLKS IILLNSGVY 
TFLSSTLKS LEEKDHIHR VLDKITDTL 
IHLMAKAGL TLQQQHQRL AQLLLILSH 
IRHMSNKGM EHLYSMKCK NVVPLYDLL 
LEMLDAHRL HAPTSRGGA SVEETDQSH 
LATAGSTSS HSLQKYYIT GEAEGFPAT 
V
UniProt P03372-1

Binding hormones

  • estradiol
    • ER-alpha binds 17beta-estradiol. [16]
    • Estrogens modulate many osteoblastic activities like the regulation of cytokine and growth factor expression, the modulation of osteoblast proliferation, differentiation, and matrix synthesis. [12]

Anatomical structures with this receptor

  • granulosa_cell

    Induced phenotypes

    • reproduction
    • ovarian follicle development
      • Higher ER alpha gene expression in granulosa cells in patients with endometriosis, compared with patients with tubular infertility, implies that endometriosis may cause ovarian dysfunction. [17]

  • cell_of_endometrium_of_uterus

    Influences

    • positive IL-11
      • IL-11 secretion is reduced by co-culture with estrogen and progesterone but stimulated by estrogen alone. [18]
    • positive VEGF-165
      • 17beta-estradiol (E2) directly regulates VEGF gene transcription in endometrial cells. [19]
      • A 2-fold increase in steady-state VEGF mRNA was evident after 15 h of E2. [19]

  • hippocampus

    Induced phenotypes

    • positive regulation of synaptic plasticity
      • studies of rodent hippocampus have highlighted the importance of estrogen receptors, particularly ER alpha as mediators of synaptic plasticity. [20]

  • eccrine_sweat_glands

    Induced phenotypes

    • regulation of cellular calcium homeostasis
      • The treatment of human eccrine sweat gland cell line NCL-SG3 with estrogen receptor antagonist suggests a role for the estrogen receptor in the release of intracellular calcium from ryanodine-receptor-gated stores. 17beta-estradiol rapidly activates an PKC isoform, PKA and Erk1/2 MAPK in a PKC-delta and estrogen-receptor-dependent manner. [21]

  • sebaceous_glands

    Induced phenotypes

    • sebaceous gland development
      • Systematically administered estrogen elicits a reduction in the size and secretion of sebaceous glands both in men and women, but this effect is usually achieved only with doses that exceed the physiologic requirement of women and produce feminization in men. [22]

  • epidermis

    Induced phenotypes

    • regulation of water loss via skin
      • The positive effects of estrogens on the water content of the skin, that were observed in all patients, may be due to dermal and epidermal components. The estrogen-stimulated increases of acid mucopolysaccharides and of hyaluronic acid contribute to an increase water content in the dermis. The increased epidermal water content may be due to increased epidermal skin thickness with subsequently elevated amounts of a natural moisturizing factor. [23]
    • wound healing
      • ER alpha is expressed in various cell-types and compartments of the penis, including the epidermis of glans penis. [24]
      • Estrogen plays a role in maintaining the glans penis integrity, in part, by facilitating penile healing, possibly via up-regulating levels of VEGF. [25]

  • hair_follicle

    Induced phenotypes

    • hair growth
      • Estrogens appear to stimulate hair growth in man, via prolonging the anagen phase of scalp hair growth by increasing cell proliferation rates and postponing their transition to the telogen phase. [26]
      • In the murine hair cycle ER alpha expression is maximal in tthe telogen follice. [27]

  • growth_plate

    Induced phenotypes

    • regulation of pubertal skeletal growth
      • Estrogen is essential for normal pubertal skeletal growth and epiphyseal maturation in both males and females. [28]
    • positive regulation of bone mineralization
      • Estrogen is the major hormone responsible for the acquisition and maintenance of bone mass in male and female. [28]
    • positive regulation of ossification
      • ER alpha is expressed in the growth-plate cartilage and in bone. [29]
      • In aging men, estradiol is the dominant sex steroid regulating bone resorption, whereas both estradiol and testosterone are important in maintaining bone formation. [30]

  • osteoblast

    Influences

    • positive IGF-1
      • Human fetal osteoblast cells (hFOB/ER9) with E2 increased steady state levels of IGF-I mRNA in a time- and dose- dependent fashion with a maximal increase of 319% +/- 33% (P < 0.01) of control occurring after treatment with 10(-7) M E2 for 48 hours. [31]
    • positive IGFBP-4
      • Treatment with E2 at 0.01-10 nM for 48 h increased IGFBP-4 mRNA to 346% +/- 90% (mean +/- SE) of control (p < 0.05) and IGFBP-4 protein to 278% +/- 75% of control (p < 0.01) in a dose-dependent fashion. [31]

    Induced phenotypes

    • antiapoptotic effect
      • The membrane localization of ER alpha and its interaction with caveolin-1 are required for stretching-induced external signal-regulated kinases (ERKs) activation and anti-apoptosis in osteocytes and osteoblasts. [32]

  • prostate

    Induced phenotypes

    • prostate cancer
      • In a prostasphere model using normal human prostate stem/progenitor cells expressing estrogen receptors it was shown that estrogens initiate and promote prostatic carcinogenesis in an androgen-supportet environment. [33]

  • arcuate_nucleus_of_hypothalamus

    Influences

    • negative metastin
      • Estradiol and testosterone down-regulate Kiss1 mRNA in the Arc. [34]

    Induced phenotypes

    • regulation of synapse organization
      • Estrogen has a facilitatory effect on the formation of new spine synapses in the arcuate neurons, reflecting a circuit remodeling in the ARC after estrogen treatment. [35]
      • 17ß-estradiol administration lead to changes in the neuronal membrane ultrastructure within the ARC. [36]

  • lung

    Induced phenotypes

    • bronchial asthma
      • Estrogen seems to have a strong promoting effect on pathogenesis of bronchial asthma via ER alpha. [37]

  • kidney

    Induced phenotypes

    • diabetic glomerulosclerosis
      • Estrogen via stimulation of ER alpha activates signaling pathways and regulates gene in glomerular/mesangiel clls in a manner that is protective against glomerulosclerosis. [38]
      • Estrogen deficiency accelerates the progression of the development of glomerulosclerosis. [39]

  • adrenal_gland

    Induced phenotypes

    • adrenal gland function
      • Estrogen receptor (ERs) were found in the adrenal gland of rats. Further, ERs were found to be localised within cell nucleo of adrenal cortex of rhesus monkey and sheep. ER alpha was detected in the adrenal zona glomerulosa, fasciculata and reticularis in the mare adrenal gland. These results suggest estradiol may affect basal adrenal function. [40]

  • mammary_gland

    Induced phenotypes

    • mammary gland development
      • ER alpha signaling is essential for the development of the adult mammary gland. ER alpha knock out mice lack the development that occurs during pre- and postpubertal stages. [41]
      • Due to its ability to stimulate proliferation ER alpha is also a driving force during mammary gland tumorigenesis. [42]

  • uterus

    Influences

    • negative testosterone
      • Female estrogen receptor knock out mice develop glomerulosclerosis at 9 months of age due to excessive ovarian testosterone production and secretion. [43]

  • breast

    Influences

    • negative adiponectin
      • Bisphenol A and estrogen suppress adiponectin release from human breast, subcutaneous, and visceral adipose tissue explants and mature adipocytes. [44]
      • Bisphenol A binds both estrogen receptors alpha and beta. [45]

  • osteoclast

    Induced phenotypes

    • negative regulation of osteoclast proliferation
      • Estrognes attenuate osteclastogenesis and life span and stimulate osteoclast apoptosis via cell-autonomous actions mediated by DNA binding-independent action of ER alpha. [46]
    • positive regulation of ossification
      • Activation of Er alpha results in preserved tickness and number of trabeculae and preserved thickness and volumetric density of cortical bone. [29]
      • ER alpha but not ER beta or AR is of importance for the trabecular bone-sparing effect of estrogens. [29]

  • placenta

    Influences

    • positive leptin
      • Estradiol upregulates leptin expression in placental cells. This effect probably involves both genomic and nongenomic actions via crosstalk between ER alpha and MAPK and PI3K signal transduction pathways. [47]

  • basophil_gonadotroph_cell_of_anterior_pituitary_FSH

    Influences

    • FSH
      • The action of estradiol is dependent upon its concentration. It can either increase or decrease the responsiveness to GnRH. [48]
    • LH
      • Action of estradiol is dependent upon its concentration. It can either in- or decrease the cells' responsiveness to GnRH. [48]

  • liver

    Influences

    • positive CBG
      • Our results show that o,p′-DDD (mitotane) increases CBG expression and secretion by an ERα-dependent mechanism. [49]

    Induced phenotypes

    • mediation of effects from thymus on liver
      • The thymus plays an important role in maintaining the drug-metabolizing enzyme activity, anti-oxidative ability and biomembrane integrity in the liver of rats. These effects are mediated by sex hormones. Estrogen mainly mediates the effect of the thymus on liver anti-oxidative functions in female rats. [50]

  • macrophage

    Induced phenotypes

    • regulation of inflammatory response
      • ER alpha is critical for maintenance of macrophage metabolism and for macrophage IL-4 responsiveness. [51]
      • ER alpha is necessary for the repression of inflammation, maintenance of oxidative metabolsim and full phagocytic activity in isolated macrophages. [51]

  • Leydig_cell_of_testis

    Induced phenotypes

    • steroidogenesis
      • Estrogen regulates steroidogenesis by acting through ER alpha and ER beta in the Leydig cells. [52]
Reference