HORMONAL RESPONSIVENESS OF POSTMENOPAUSAL MAMMARY GLAND

绝经后乳腺的激素反应

• 批准号: 2054956
• 负责人: SANDRA Z HASLAM
• 金额: $ 17.25万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2054956
• 关键词: autoradiography; biopsy; cell cycle; cell growth regulation; epidermal growth factor; estrogen receptors; estrogens; growth factor receptors; growth inhibitors; hormone regulation /control mechanism; hormone therapy; human subject; immunocytochemistry; insulinlike growth factor; laboratory mouse; mammary epithelium; mammary gland; postmenopause; progesterone receptors; progestins; receptor expression; stromal cells; transforming growth factors

Little in known about the mitogenic effects of estrogen (E) and progestins (P) in the postmenopausal breast. Despite this, hormones are commonly prescribed for postmenopausal hormone replacement therapy (HRT). We have developed an in vivo model of the postmenopausal mammary gland in mice and preliminary studies show that epithelial and stromal cells of the postmenopausal mammary gland of the mouse have a heightened sensitivity to the growth promoting effects of E and stromal cells in particular, have decreased expression of the growth inhibitor, TGF-Beta1 after estrogen treatment. The overall goals of this proposal are to characterize the hormonal responsiveness of the postmenopausal gland in mice to ovarian hormones and to elucidate the underlying mechanism(s). We hypothesize that in the mouse, altered hormonal responsiveness to estrogen may be due to either increased potency or efficacy of the hormone as a result of altered receptor function or an increase in receptor number, respectively. Furthermore, altered responsiveness to progestins, altered expression of growth factors (EGF, TGF-alpha, IGF-I, II) growth inhibitors (TGF-Beta1) and/or their respective receptors will also be investigated in the postmenopausal mammary gland, since interactions between estrogen and progestins and ovarian hormones and growth factors/inhibitors are also involved in growth regulation. To determine if a similar situation exists in the human, hormone receptor and growth factor/inhibitor, cellular distribution, as well as the effects of HRT on mammary cell proliferation and mammary gland morphology will also be analyzed in the postmenopausal human breast. The results obtained from the proposed studies should provide important information about the biology of the postmenopausal mammary gland and potential consequences of hormone replacement treatment in postmenopausal women.

关于雌激素（E）和 绝经后乳房中的孕激素（P）。 尽管如此，激素是 通常用于绝经后激素替代疗法（HRT）。 我们已经开发了绝经后乳腺的体内模型 在小鼠和初步研究中，上皮细胞和基质细胞 小鼠的绝经后乳腺的增长 对E和基质细胞在生长中的敏感性 特别，生长抑制剂TGF-BETA1的表达降低 雌激素治疗后。 该提议的总体目标是 表征绝经后的激素反应性 小鼠到卵巢激素并阐明基本机制。 我们假设在小鼠中，激素反应性改变了 雌激素可能是由于效力提高或疗效 受体功能改变或增加 受体编号分别。 此外，对 孕激素，生长因子的表达改变（EGF，TGF-Alpha，IGF-I， ii）生长抑制剂（TGF-BETA1）和/或其各自的受体将 也可以在绝经后乳腺中进行研究，因为 雌激素与孕激素以及卵巢激素之间的相互作用以及 生长因子/抑制剂也参与生长调节。 到 确定人类中是否存在类似情况，激素受体 和生长因子/抑制剂，细胞分布以及 HRT对乳腺细胞增殖和乳腺形态的影响 也将在绝经后的人类乳房中进行分析。 结果 从拟议的研究中获得的应提供重要信息 关于绝经后乳腺的生物学和潜力 绝经后妇女激素替代治疗的后果。