Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Menopause. 2011 Sep;18(9):1001-9. doi: 10.1097/gme.0b013e3182127c9b.
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.
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.
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.
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.
本研究旨在比较长期激素治疗后绝经猴正常子宫和乳腺中环氧化酶（COX）1 和 COX-2 的分布和免疫反应性。
雌性成年食蟹猴在开始激素治疗前 3 个月双侧卵巢切除术。动物接受（实验 1）结合雌激素（CEE）、醋酸甲羟孕酮（MPA）、CEE+MPA 或他莫昔芬治疗或指定为对照（C）。在实验 2 中，动物接受 CEE、CEE+MPA 或替勃龙治疗或指定为 C。收集、固定和石蜡包埋乳腺组织和子宫。进行 COX-1 和 COX-2 的免疫组织化学检测。
COX-1 免疫染色在子宫内膜基质中被他莫昔芬和 CEE 治疗下调，在子宫肌层中被 CEE+MPA 下调。乳腺上皮的 COX-1 免疫染色被 CEE+MPA 下调，而乳腺中的其他细胞类型似乎较少受激素治疗影响。子宫内膜基质中的 COX-2 免疫反应性增加 CEE+MPA。在腺上皮中，与仅接受 CEE 治疗和未接受任何治疗（C）相比，CEE+MPA 和替勃龙治疗增加了 COX-2 免疫染色。在子宫肌层中未发现激素治疗对 COX-2 免疫染色的影响。在实验 2 中，与未治疗（C）相比，CEE 治疗后乳腺腺上皮中的 COX-2 免疫染色增加。在乳腺中未发现激素治疗对 COX-2 表达的其他影响。
我们的结果表明，COX-1 和 COX-2 在去卵巢猴的正常子宫和乳腺中分布和受激素调节不同。COX-1 在子宫中占优势，而 COX-2 在乳腺中占优势。
