DIRECT GONADOTROPIN REGULATION OF HUMAN FALLOPIAN TUBES

人类输卵管，以前从未被认为是 人绒毛膜促性腺激素/促黄体生成素调节的直接靶点，表达hCG及其受体基因。 这些基因的表达取决于大脑的解剖区域 女性的输卵管和生殖状态。输卵管粘膜，经历了 细胞分裂，并活跃于大分子合成和分泌， 比其他任何输卵管细胞层表达得更多。输卵管组织孵化 高纯度hCG可引起剂量和时间依赖性增加 催化活性的5-脂氧合酶、环氧合酶(COX)-1和COX-2 输卵管粘膜中的酶。这些发现表明hCG和LH可以 调节不依赖卵巢类固醇激素的输卵管粘膜功能。 然而，这些激素和生长之间可能存在相互作用。 影响管子整体调节的因素。目前的赠款申请 建议研究：1)外源性和内源性hCG和 其受体在粘膜细胞分裂和大分子合成中的作用 2)输卵管hCG及其受体是否受卵巢调节 类固醇激素、生长因子和人绒毛膜促性腺激素/黄体生成素；3)什么信号机制 和介质参与hCG的作用以及4)最终卵巢是否 类固醇激素和生长因子可以模拟和/或改变hCG的作用。 将测试hCG和HLH的功能等价性，因为这两个 激素是结构和功能上的同系物，它们结合在一起 感受器。将只使用分泌期的输卵管粘膜，因为它 丰富地共表达hCG及其受体，这种表达是 与其他生殖状态相比，分泌期更高。这些 研究将借助反义cdna表达技术， 其他分子生物学、细胞生物学和生化技术。这个 这项建议的总体目标是促进我们目前对 人绒毛膜促性腺激素及其受体在输卵管和输卵管中的作用及调节 将输卵管功能的所有潜在调节器放在适当的 透视。这些知识可以进一步促进对hCG/LH的研究 输卵管功能的调节，因为它可能与早期的许多事件有关 妊娠、体外受精、异位妊娠和盆腔 炎症性疾病。此外，它还可能导致 输卵管避孕或治疗不孕症的新方法 输卵管功能障碍。有足够的绝经前输卵管组织 女性，包括少数族裔受试者，正在接受输卵管结扎术或 将可以进行子宫切除术。拟议中的研究以前从未进行过 在人类或其他物种的输卵管或子宫上进行过手术。

Human fallopian tubes, which have never previously been considered a direct target of hCG/LH regulation, express hCG and its receptor genes. The expression of these genes is dependent on the anatomical region of the tube and reproductive state of the women. Tubal mucosa, which undergoes cell division and is active in macromolecular synthesis and secretion, expresses more than any other tubal cell layer. Incubation of tubal tissue with highly purified hCG resulted in a dose and time dependent increase of catalytically active 5-lipoxygenase, cyclooxygenase (COX)-1 and COX-2 enzymes in tubal mucosa. These findings suggest that hCG and LH can regulate tubal mucosal functions independent of ovarian steroid hormones. However, there may be interactions between these hormones and growth factors in overall regulation of tubes. The present grant application proposes to investigate: 1) the role of exogenous and endogenous hCG and its receptor in mucosal cell division and macromolecular synthesis and secretion; 2) whether tubal hCG and its receptors are regulated by ovarian steroid hormones, growth factors and hCG/LH; 3) what signaling mechanisms and mediators are involved in hCG action and 4) finally whether ovarian steroid hormones and growth factors can mimic and/or modify hCG action. Functional equivalency of hCG and hLH will be tested because these two hormones are structural and functional homologs that bind to the same receptors. Only tubal mucosa from secretory phase will be used because it abundantly co-expresses hCG and its receptors and this expression is higher in secretory phase as compared to other reproductive states. These investigations will be aided by antisense cDNA expression technology, other molecular biology, cell biology and biochemical techniques. The overall goal of this proposal is to advance our current understanding of the role and regulation of hCG and its receptors in fallopian tubes and to place all the potential regulators of fallopian tube functions in a proper perspective. Such knowledge can further stimulate research on hCG/LH regulation of tubal functions as it may relate to numerous events of early pregnancy, in vitro fertilization, ectopic pregnancy and pelvic inflammatory disease. In addition, it could lead to the development of newer methods of tubal contraception or treatment of infertility due to tubal dysfunction. Adequate amounts of tubal tissue from premenopausal women, including minority subjects, undergoing tubal ligation or hysterectomy will be available. The proposed studies have never previously been performed on fallopian tubes or uteri of humans or other species.