title: Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation.
abstract: BACKGROUND
  Endometriosis, pro-inflammatory and invasive benign disease estrogen dependent, abnormally express in endometria the enzyme P450Arom, positively regulated by steroid factor-1 (SF-1). Our objective was to study the nuclear protein contents of upstream stimulating factor 2 (USF2a and USF2b), a positive regulator of SF-1, throughout the menstrual cycle in eutopic endometria from women with and without (control) endometriosis and the involvement of nuclear estrogen receptors (ER) and G-coupled protein estrogen receptor (GPER)-1.
  
  
  RESULTS
  Upstream stimulating factor 2 protein contents were higher in mid (USF2b) and late (USF2a and USF2b) secretory phase in eutopic endometria from endometriosis than control (p < 0.05). In isolated control epithelial cells incubated with E2 and PGE2, to resemble the endometriosis condition, the data showed: (a) significant increase of USF2a and USF2b nuclear protein contents when treated with E2, PPT (specific agonist for ERα) or G1 (specific agonist for GPER1); (b) no increase in USF2 binding to SF-1 E-Box/DNA consensus sequence in E2-treated cells; (c) USF2 variants protein contents were not modified by PGE2; (d) SF-1 nuclear protein content was significantly higher than basal when treated with PGE2, E2 or G1, stimulation unaffected by ICI (nuclear ER antagonist); and (e) increased (p < 0.05) cytosolic protein contents of P450Arom when treated with PGE2, E2, PPT or G1 compared to basal, effect that was additive with E2 + PGE2 together. Nevertheless, in endometriosis cells, the high USF2, SF-1 and P450Arom protein contents in basal condition were unmodified.
  
  
  CONCLUSIONS
  These data strongly suggest that USF2 variants and P450Arom are regulated by E2 through ERα and GPER1, whereas SF-1 through GPER1, visualized by the response of the cells obtained from control endometria, being unaffected the endogenously stimulated cells from endometriosis origin. The lack of E2 stimulation on USF2/SF-1 E-Box/DNA-sequence binding and the absence of PGE2 effect on USF2 variants opposite to the strong induction that they exert on SF1 and P450 proteins suggest different mechanisms and indirect regulations. The sustained USF2 variants protein expression during the secretory phase in eutopic endometria from women with endometriosis may participate in the pathophysiology of this disease strongly associated with infertility and its characteristic endometrial invasion to ectopic sites in the pelvic cavity.
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. jazmin.castro@gmail.com.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Castro
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. garayarecabal@gmail.com.
authors.forename: Germán
authors.initials: G
authors.lastname: Araya
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. pamela.inostrozab@usach.cl.
authors.forename: Pamela
authors.initials: P
authors.lastname: Inostroza
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. paulina.hidalgo.g@gmail.com.
authors.forename: Paulina
authors.initials: P
authors.lastname: Hidalgo
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. reinaldogonzalezr@yahoo.com.|San Borja-Arriarán Clinical Hospital, Santiago, Chile. reinaldogonzalezr@yahoo.com.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: González-Ramos
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. hsovino@yahoo.com.|San Borja-Arriarán Clinical Hospital, Santiago, Chile. hsovino@yahoo.com.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sovino
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. mboric@med.uchile.cl.
authors.forename: M Angélica
authors.initials: MA
authors.lastname: Boric
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. fuentesarielster@gmail.com.|San Borja-Arriarán Clinical Hospital, Santiago, Chile. fuentesarielster@gmail.com.
authors.forename: Ariel
authors.initials: A
authors.lastname: Fuentes
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, P.O. Box 226-3, Santiago, Chile. cjohnson@med.uchile.cl.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001141:Aromatase / Q000378:metabolism*; D001706:Biopsy; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008597:Menstrual Cycle / Q000378:metabolism; D061251:Primary Cell Culture; D018709:Statistics, Nonparametric; D051720:Upstream Stimulatory Factors / Q000378:metabolism*
chemical_list: C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors; D004958:Estradiol; D001141:Aromatase