STEROID & RETINOID EFFECTS ON FEMALE REPRODUCTIVE TRACT

尽管有大量证据表明维甲酸和性行为 类固醇对女性生殖道组织的调节作用 这种影响还没有在分子水平上得到检验。考虑到潜在的 这些化合物之间相互作用的重要性，我们建议 为了验证维甲酸对生长和生长有直接影响的假设 人子宫细胞的体外分化及其可能 调控性类固醇、雌二醇和孕酮的作用 (P)维甲酸和类固醇对细胞生长和分化的影响 人类子宫内膜和宫颈细胞将在培养系统中进行检测 之所以被选中，是因为它们已被证明可以促进 分化功能：1)在3T3饲养层上单层生长 细胞，一种已被证明在促进 上皮细胞的生长分化和2)重组细胞的生长 子宫/宫颈上皮细胞和间质细胞的培养及孵化 胶原蛋白筏，一种已被有效用于增强 与各种各样的上皮细胞类型的体外分化， 培养物在体内的保留表型将通过以下方式进行评估 子宫内膜各种分化相关标志物的测定 可由维甲酸和类固醇调节的功能；1)细胞 E_2和P受体含量，2)维甲酸结合蛋白含量，30 细胞角蛋白的水平和类型以及4)含量和 转谷氨酰胺酶活力。从培养细胞中获得的图谱 将与从新分离的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，以检查的影响 维甲酸及其对人子宫中雌二醇和孕激素的调节作用 疾病。这些研究的短期目标是开发基础 对维甲酸和类固醇在女性中相互作用的认识 生殖组织。长期目标是确定佐剂是否 类维A酸类药物是治疗雌孕激素的有效手段 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.