title: Distribution of cyclooxygenases 1 and 2 in the uterus and breast of cynomolgus monkeys-effects of hormone treatment.
abstract: OBJECTIVE
  The aim of this study was to compare the distribution and immunoreactivity of cyclooxygenase (COX) 1 and COX-2 in normal uterus and breast after long-term hormone therapy in postmenopausal monkeys.
  
  
  METHODS
  Female adult cynomolgus macaques were bilaterally ovariectomized 3 months before the initiation of hormone treatment. The animals were either treated (experiment 1) with conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, or tamoxifen or designated as controls (C). In experiment 2, the animals were either treated with CEE, CEE + MPA, or tibolone or designated as C. Breast tissue and uteri were collected, fixed, and paraffin embedded. Immunohistochemistry assays for COX-1 and COX-2 were performed.
  
  
  RESULTS
  COX-1 immunostaining was decreased by tamoxifen and CEE treatment in the endometrial stroma and by CEE + MPA in the myometrium. COX-1 immunostaining of the breast epithelia was down-regulated by CEE + MPA, whereas other cell types in the breast seem to be less affected by hormone treatment.COX-2 immunoreactivity in the endometrial stroma was increased by CEE + MPA. In the glandular epithelium, CEE + MPA and tibolone treatment increased COX-2 immunostaining compared with CEE treatment only and no treatment at all (C). No effect from hormone treatment on COX-2 immunostaining was found in the myometrium. COX-2 immunostaining in the glandular epithelium of the breast was, in experiment 2, increased after CEE treatment compared with no treatment (C). No other effects by hormone therapy on COX-2 expression were found in the breast.
  
  
  CONCLUSIONS
  Our results show that COX-1 and COX-2 are differently distributed and regulated by hormones in the normal uterus and breast of ovariectomized macaques. COX-1 is prevailing in the uterus, whereas COX-2 is dominant in the mammary gland.
authors.affiliation: Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: von Schoultz
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
authors.forename: Lena
authors.initials: L
authors.lastname: Sahlin
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D010052:Ovariectomy; D010053:Ovary / Q000378:metabolism / Q000601:surgery; D013629:Tamoxifen / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004966:Estrogens, Conjugated (USP); D013629:Tamoxifen; D017258:Medroxyprogesterone Acetate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2