title: GPER and ERα expression in abnormal endometrial proliferations.
abstract: G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions.
  
  
  CONCLUSIONS
  The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.
authors: Department of Mother and Child, University of Medicine and Pharmacy of Craiova, Romania; oana.banica@umfcv.ro, oanabanica25@yahoo.com.
authors: Andrei Adrian
authors: AA
authors: Tica
authors: Oana Sorina
authors: OS
authors: Tica
authors: Claudia Valentina
authors: CV
authors: Georgescu
authors: Daniel
authors: D
authors: Pirici
authors: Maria
authors: M
authors: Bogdan
authors: Tudorel
authors: T
authors: Ciurea
authors: Stelian ŞtefăniŢă
authors: SŞ
authors: Mogoantă
authors: Corneliu Cristian
authors: CC
authors: Georgescu
authors: Alexandru Cristian
authors: AC
authors: Comănescu
authors: Tudor Adrian
authors: TA
authors: Bălşeanu
authors: Raluca Niculina
authors: RN
authors: Ciurea
authors: Eugen
authors: E
authors: Osiac
authors: Ana Maria
authors: AM
authors: Buga
authors: Marius Eugen
authors: ME
authors: Ciurea
mesh_terms: D049109:Cell Proliferation; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled