title: Estradiol induces heparanase-1 expression and heparan sulphate proteoglycan degradation in human endometrium.
abstract: BACKGROUND
  This study seeks to determine whether estrogen is able to regulate the expression of heparanase-1 (HPR1) in human endometrium.
  
  
  METHODS
  HPR1 expression and heparan sulphate (HS) deposition in the endometrium collected in various menstrual phases were analysed by immunohistochemical and immunofluorescence staining, respectively. HPR1 expression in the endometrial cells unexposed or exposed to estradiol was analysed by using RT-PCR and luciferase reporter assay. HPR1 activity was analysed by using a novel enzyme-linked immunosorbent assay (ELISA). Cell surface HS levels were analysed by flow cytometry. Serum HPR1 activity in women receiving follicle-stimulating hormone (FSH) for IVF was measured by ELISA.
  
  
  RESULTS
  HPR1 expression was rarely detected in the endometrium in the early and mid-proliferative phases but was increased in the late proliferative phase and in the secretory phases. HPR1 expression was negatively associated with HS in the basement membrane (BM) of the endometrial glands. HPR1 gene expression, HPR1 promoter activity and HPR1 enzymatic activity were increased in the endometrial cells when exposed to 17beta-estradiol (E(2)), whereas cell surface HS levels showed a decrease which could be blocked by PI-88, an HPR1 inhibitor. Serum HPR1 levels were increased in women with moderately elevated blood estrogen levels after receiving FSH.
  
  
  CONCLUSIONS
  HPR1 is differentially expressed in the endometrium in different menstrual phases. Estrogen plays an important role in inducing HPR1 expression, subsequently leading to HS degradation on the endometrial cell surface and in the BM of the endometrium.
authors.affiliation: Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, USA. xxu@rush.edu
authors.forename: Xiulong
authors.initials: X
authors.lastname: Xu
authors.forename: Jianchi
authors.initials: J
authors.lastname: Ding
authors.forename: Geetha
authors.initials: G
authors.lastname: Rao
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Prinz
authors.forename: Nasir
authors.initials: N
authors.lastname: Rana
authors.forename: W Paul
authors.initials: WP
authors.lastname: Dmowski
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D005966:Glucuronidase / Q000096:biosynthesis* / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle; D008856:Microscopy, Fluorescence; D016471:Ovarian Hyperstimulation Syndrome / Q000378:metabolism; D000099175:Heparanase
chemical_list: D004958:Estradiol; D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D000099175:Heparanase