HORMONAL RESPONSIVENESS OF POSTMENOPAUSAL MAMMARY GLAND

对雌激素（E）和雌激素受体（ER）的促有丝分裂作用知之甚少。 孕激素（P）在绝经后乳房。 尽管如此，荷尔蒙 通常用于绝经后激素替代疗法（HRT）。 我们已经建立了一个绝经后乳腺的体内模型 初步研究表明上皮细胞和基质细胞 绝经后的小鼠乳腺中， 对E和基质细胞的生长促进作用的敏感性， 特别是生长抑制因子TGF-β 1的表达降低 雌激素治疗后。 本提案的总体目标是 表征绝经后腺体的激素反应性， 小鼠的卵巢激素，并阐明潜在的机制。 我们假设，在小鼠中， 雌激素可能是由于增加的效力或功效， 由于受体功能改变或 受体数目。 此外，改变了对 孕激素，生长因子（EGF，TGF-α，IGF-I， II）生长抑制剂（TGF-β 1）和/或它们各自的受体， 也可以在绝经后乳腺中进行研究，因为 雌激素和孕激素与卵巢激素之间的相互作用， 生长因子/抑制剂也参与生长调节。 到 确定人类是否存在类似的情况，激素受体， 和生长因子/抑制剂，细胞分布，以及 HRT对乳腺细胞增殖及乳腺形态的影响 也将在绝经后人乳腺中进行分析。 结果 从拟议的研究中获得的信息应提供重要信息， 绝经后乳腺的生物学和潜在的 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.