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首页> 外文学位 >Effects of continuous and cyclic combined oral contraceptives on mouse mammary gland structure.
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Effects of continuous and cyclic combined oral contraceptives on mouse mammary gland structure.

机译：连续和循环联合口服避孕药对小鼠乳腺结构的影响。

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摘要

The breast goes through cycles of expansion, differentiation, and regression with every estrous/menstrual cycle, driven by hormonal stimulation followed by hormone withdrawal. The number of cycles over a lifetime is positively associated with breast cancer risk; this increased risk may be the result of hormone-stimulated epithelial growth, inflammatory tissue remodeling processes during hormone withdrawal, or both. The use of cyclic combined oral contraceptive (cyclic COC) regimen, that incorporates a hormone withdrawal period in each cycle, is associated with increased risk of ER/PR negative breast cancer, particularly in current COC users, and women who started COC use early in life. In contrast, the effect of extended-use (i.e., continuous) OC on mammary gland structure or breast cancer risk has not been evaluated. The purpose of the current study was to test the hypothesis that extended OC provides protection against breast cancer, by removing the hormone withdrawal phase associated with both cyclic OC and normal cycling. Starting at day 50 of age (to mimic COC exposure in young women), BALB/C mice were fed a fresh liquid diet daily containing no OC, or ethinyl estradiol and levonorgestrel, either continuously for 28 days, or as a cyclic regimen (three days OC, followed by one day basal liquid diet). After 28 days, 10 mice per group were sacrificed and mammary glands dissected for whole mount and histologic analysis. The extended OC group showed an average increase in epithelial density of 65% compared to control; the cyclic group was increased by 13%. However this increased epithelial density in both OC regimens was associated with more differentiated state, with a decrease in terminal end buds, TEB, frequency balanced by an increase in alveolar buds, and a trend towards increased ductal secretions. Cyclic OC increased Ki-67 staining in small mammary ducts (epithelium plus stroma). These suggest that exposure to cyclic OC increase the percentage of apoptosis in the mammary gland cells, which could be related to an increase of breast cancer risk. Both OC regimens increased the number of cells infiltrating the mammary adipose stroma. These results suggest that short-term exposure to continuous COC can induce a more differentiated state in nonparous mouse mammary glands, with a higher differentiation in continuous OC than in cyclic OC. At this point there is no in vivo evidence that suggest that extended OC provides protection against breast cancer, but this data suggests that continuous OC may protect against carcinogenic exposure.
机译：在荷尔蒙刺激和激素撤除的驱动下，乳房在每个发情/月经周期经历扩张，分化和消退的周期。一生中的周期数与乳腺癌风险呈正相关；这种增加的风险可能是激素刺激的上皮生长，激素戒断过程中炎症组织重塑过程或两者的结果。循环联合口服避孕药（循环COC）方案的使用，在每个周期中都包含激素停药期，与ER / PR阴性乳腺癌的风险增加相关，尤其是在目前的COC使用者和早期开始使用COC的女性中生活。相反，尚未评估长期使用（即连续使用）OC对乳腺结构或乳腺癌风险的影响。本研究的目的是通过消除与周期性OC和正常循环相关的激素戒断阶段来检验延长OC可预防乳腺癌的假说。从年龄50天开始（模拟年轻女性的COC暴露），每天向BALB / C小鼠喂食不含OC或乙炔雌二醇和左炔诺孕酮的新鲜流质饮食，连续28天或以循环方案喂养（三只）天OC，然后一日进行基础流质饮食）。 28天后，处死每组10只小鼠，并解剖乳腺以进行整个安装和组织学分析。与对照组相比，扩展OC组的上皮密度平均增加了65％。循环组增加了13％。然而，这两种OC方案中上皮密度的增加与分化状态更加相关，末端芽，TEB的减少，肺泡芽的增加所平衡的频率以及导管分泌物增加的趋势。循环OC增加了小乳腺导管（上皮加基质）中Ki-67的染色。这些提示暴露于循环OC会增加乳腺细胞凋亡的百分比，这可能与乳腺癌风险增加有关。两种OC方案均增加了渗入乳腺脂肪基质的细胞数量。这些结果表明，短期暴露于连续COC可以在未产小鼠乳腺中诱导更高分化的状态，与循环OC相比，连续OC的分化程度更高。在这一点上，没有体内证据表明延长的OC可预防乳腺癌，但是该数据表明持续的OC可以预防致癌性暴露。

著录项

  • 作者

    Esteves-Natal, Evelyn.;

  • 作者单位

    State University of New York at Buffalo.;

  • 授予单位 State University of New York at Buffalo.;
  • 学科 Biology Molecular.;Engineering Biomedical.
  • 学位 M.S.
  • 年度 2014
  • 页码 134 p.
  • 总页数 134
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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