Dissecting Uterine Progesterone Resistance

描述(申请人提供)：黄体酮是一种类固醇激素，对女性生殖道具有重要作用，对生殖至关重要。其中关键的作用是刺激子宫内膜间质细胞的增殖和分化。子宫不能对黄体酮作出适当反应(称为黄体酮抵抗)是许多女性生殖道疾病的特征，包括子宫内膜异位症、多囊卵巢综合征、子宫内膜增生症/癌症和早孕丢失。在理解孕激素抵抗的病因方面取得进展的障碍是合适的实验模型的可用性。棕色挪威(BN)大鼠是一种近亲繁殖的品系，是一种新发现的研究孕激素抵抗的动物模型。BN大鼠孕酮抵抗与各种人类女性生殖道疾病中描述的黄体酮抵抗非常相似。我们提出的研究的目标是阐明导致子宫孕酮抵抗的细胞和分子过程。我们建议研究BN大鼠的孕酮抵抗。拟议的研究工作将提供有关孕酮耐药的分子机制的信息，包括剖析单个染色体对子宫孕酮耐药表型的贡献。了解子宫孕酮抵抗的分子机制是确定发育敏感事件的关键，这些事件可能容易受到调节失调的影响；并代表着新的科学和应用追求的机会，包括诊断的发展，特别是孕酮抵抗引起的疾病的治疗。

DESCRIPTION (provided by applicant): Progesterone is a steroid hormone with important actions on the female reproductive tract that are essential for reproduction. Among these key actions are stimulation of uterine endometrial stromal cell proliferation and differentiation. Failure in the ability of the uterus to appropriately respond to progesterone (referred to as progesterone resistance) is a characteristic feature of a number of female reproductive tract disorders, including endometriosis, polycystic ovarian syndrome, endometrial hyperplasia/cancer, and early pregnancy loss. The barrier for progress in understanding the etiology of progesterone resistance is the availability of appropriate experimental models. The Brown Norway (BN) rat is an inbred strain and a newly discovered animal model for investigating progesterone resistance. BN rat progesterone resistance is remarkably similar to progesterone resistance described in various human female reproductive tract diseases. The goal of our proposed research is to elucidate cellular and molecular processes causing uterine progesterone resistance. We propose to investigate progesterone resistance in the BN rat. The proposed research efforts will provide information on molecular mechanisms underlying progesterone resistance, including the dissection of the contributions of individual chromosomes to the uterine progesterone resistance phenotype. Understanding molecular mechanisms underlying uterine progesterone resistance is a key to identifying developmentally sensitive events that are potentially susceptible to dysregulation; and represent opportunities for new scientific and applied pursuits, including the development of diagnostics and especially treatments for diseases stemming from progesterone resistance.