STEROID & RETINOID EFFECTS ON FEMALE REPRODUCTIVE TRACT

尽管有大量证据表明，类维生素A和性 类固醇调节女性生殖道组织， 其影响尚未在分子水平上进行研究。考虑到潜在的 这些化合物之间的相互作用的重要性，我们建议 为了检验类维生素A对生长有直接影响的假设， 人子宫细胞在体外的分化，他们可能 调节性类固醇、雌二醇（E2）和孕酮的作用 (P)类维生素A和类固醇激素对生长和分化的影响 将在培养系统中检查人子宫内膜和子宫颈细胞 选择，因为它们已被证明可以促进保留 分化功能; 1）在3 T3小鼠饲养层上作为单层生长 细胞，一个系统，已被证明是非常有用的促进 上皮细胞生长和分化以及2）重组的 子宫/宫颈上皮细胞和基质细胞的培养 胶原筏，一种有效地用于增强 用多种上皮细胞类型进行体外分化， 将通过以下方法评价培养物的体内表型保留 确定子宫内膜的各种分化依赖性标志物 可能由类维生素A和类固醇调节的功能; 1）细胞 E2和P受体含量，2）维甲酸结合蛋白含量，30 存在的细胞角蛋白的水平和类型，以及4）细胞角蛋白的含量和 转氨酶活性。从培养细胞中获得的图谱 将与新鲜分离样本中观察到的结果进行比较，以评估 体外对体内状态的保真度。 拟议中的研究结果将提供新的信息 关于这些代理之间的相互作用，并将使设计 未来的体外和体内研究， 维甲酸及其对人子宫内膜E2和P效应的调节 疾病这些研究的短期目标是发展基本的 关于类维生素A和类固醇在女性中相互作用的知识 生殖组织长期目标是确定是否有佐剂 类维生素A的使用是改变E2和P的可用治疗方式 对子宫疾病的影响。

Despite considerable evidence suggesting that both retinoids and sex steroids regulate female reproductive tract tissue the interplay of their effects has not been examined at the molecular level. Given the potential importance of interaction between these classes of compounds, we propose to test the hypothesis that retinoids have direct effects on growth and differentiation of human uterine cells in vitro and that they may modulate the effects of the sex steroids, estradiol (E2) and progesterone (P) Retinoid and steroid effects on the growth and differentiation of human endometrial and cervical cell will be examined in culture systems selected because they have been shown to promote retention of differentiated function; 1) growth as monolayers on 3T3 murine feeder cells, a system that has proven to be extremely useful in promoting epithelial cell growth and differentiation and 2) growth of recombined cultures of uterine/cervical epithelial and stromal cells on foating collagen rafts, a method that has been effectively used to enhance in vitro differentiation with a wide variety of epithelial cell types, Retention of in vivo phenotype of the cultures will be evaluated by determining various differentiation dependent markers of endometrial function that may be modulated by retinoids and steroids; 1) the cellular E2 and P receptor content, 2) the retinoid binding protein content, 30 the levels and types of cytokeratins present and 4) the content and activity of transglutaminase. Profiles obtained from the cultured cells will be compared to that observed from freshly isolated samples to assess the in vitro fidelity to the in vivo state. The results of the proposed research will provide new information concerning the interplay between these agents and will enable the design of future in vitro and in vivo studies to examine the effects of retinoids and their modulation of E2 and P effects in human uterine disease. The short-term goal of these studies is to develop basic knowledge regarding the interplay of retinoids and steroids in female reproductive tissues. The long-term goal is to determine whether adjuvant use of retinoids is available treatment modality to modify E2 and P effects in uterine disease.