HORMONAL RESPONSIVENESS OF POSTMENOPAUSAL MAMMARY GLAND

对雌激素(E)和雌激素的促有丝分裂作用知之甚少 绝经后乳房中的孕激素(P)。尽管如此，荷尔蒙还是 通常用于绝经后激素替代疗法(HRT)。 我们开发了一个绝经后乳腺的活体模型。 在小鼠身上，初步研究表明，上皮细胞和基质细胞 对绝经后的小鼠乳腺有明显的增厚作用 E细胞和基质细胞对细胞生长促进作用的敏感性 尤其是降低了生长抑制因子转化生长因子-β1的表达 在雌激素治疗后。这项提案的总体目标是 描述绝经后腺体的激素反应性 并阐明其对小鼠卵巢激素的作用机制(S)。 我们假设，在小鼠体内，荷尔蒙对 雌激素可能是由于增强了性激素的效力或功效。 由于受体功能改变或增加而引起的荷尔蒙 分别为受体编号。此外，改变了对 孕激素，改变生长因子(EGF，转化生长因子-α，IGF-I， 二)生长抑制物(转化生长因子-β1)和/或其各自的受体 也要对绝经后的乳腺进行检查，因为 雌激素、孕激素与卵巢激素的相互作用 生长因子/抑制物也参与生长调节。至 确定在人类激素受体中是否存在类似的情况 和生长因子/抑制物，细胞分布，以及 激素替代疗法对乳腺细胞增殖和乳腺形态的影响 还将在绝经后的人类乳房中进行分析。结果是 从拟议的研究中获得的信息应提供重要信息 关于绝经后乳腺的生物学和潜能 绝经后妇女激素替代治疗的后果。

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.