Effects of conjugated estrogens, medroxyprogesterone acetate, and tamoxifen on the mammary glands of macaques
Effects of conjugated estrogens, medroxyprogesterone acetate, and tamoxifen on the mammary glands of macaques
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DOI：
10.1023/a:1005984932268
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发表时间：
1998-04-01
影响因子：
3.8
通讯作者：
von Schoultz, B
中科院分区：
文献类型：
--
作者：
Cline, JM;Soderqvist, G;von Schoultz, B
这项工作的目的是在长期研究中检查成年卵巢切除雌性食蟹猴（Macaca fascicularis）的乳腺或：激素治疗对慢性疾病的影响。治疗包括结合马雌激素（CEE）、醋酸甲羟孕酮（MPA）、CEE+MPA和他莫昔芬。剂量是从那些给予妇女缩放。在饮食中给予治疗三年，然后进行尸检和组织收集。评价的终点包括乳腺组织学、组织形态学和乳腺上皮细胞增殖标记物Ki-67、雌激素受体（ER）和孕激素受体（PR）的免疫组化检测。主要结果如下：CEE诱导PR表达和局灶性至弥漫性小叶肺泡增生。MPA的加入增加了细胞的增殖，但单独使用MPA并不能诱导细胞增殖。他莫昔芬诱导ER和PR，但不诱导Ki-67表达或腺体增生。未观察到新生儿。这些研究结果表明，孕激素可能会加剧，而不是拮抗雌激素替代治疗引起的乳腺增生，他莫昔芬具有雌激素激动剂和拮抗剂的作用，在正常的灵长类动物乳腺性类固醇受体的表达。
The purpose of this work was to examine the mammary glands of adult, ovariectomized female cynomolgus macaques (Macaca fascicularis) in a long-term study or: the effects of hormone treatments on chronic disease. Treatments included conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE+MPA, and tamoxifen. Doses were scaled from those given women. Treatments were given in the diet for three years, followed by necropsy and tissue collection. Endpoints evaluated included glandular histology, histo morphometry, and immunohistochemical detection of the proliferation marker Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in mammary epithelial cells. Major findings were as follows: CEE induced PR expression and focal to diffuse lobuloalveolar proliferation. Proliferation was increased by the addition of MPA, but was not induced by MPA alone. Tamoxifen induced ER and PR but not Ki-67 expression or glandular hyperplasia. Neoplasms were not seen. These findings indicate that progestogens may exacerbate, not antagonize mammary gland proliferation induced by estrogen replacement therapy, and that tamoxifen has both estrogen agonist and antagonist effects on sex steroid receptor expression in the normal primate breast.