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Distribution of cyclooxygenases 1 and 2 in the uterus and breast of cynomolgus monkeys-effects of hormone treatment

Zhang, Hua MD, PhD1,2; Schoultz, Bo von MD, PhD3; Cline, J. Mark DVM, PhD4; Sahlin, Lena PhD1

doi: 10.1097/gme.0b013e3182127c9b
Original Articles

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.

COX-1 and COX-2 are differently distributed and regulated through hormone treatment in the healthy uterus and breast. COX-1 is more dominant in the uterus, whereas COX-2 is more prevalent in the mammary gland.

From the 1Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 3Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; and 4Wake Forest University School of Medicine Winston-Salem, NC.

Received December 3, 2010; revised and accepted January 25, 2011.

Funding/support: This study received financial support from the Swedish Research Council (project 20137 [L.S.]) and Karolinska Institutet. Financial support was also provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. The parent studies from which the tissues were collected were supported by National Institutes of Health Grants HL-490852 and HL-45666 and Organon. Hua Zhang isa postdoctoral fellow supported by the Chinese government (grant 2008850544).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Lena Sahlin, PhD, Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska University Hospital-Solna, Q2:08, Stockholm SE-171 76, Sweden. E-mail:

©2011The North American Menopause Society