DIRECT GONADOTROPIN REGULATION OF HUMAN FALLOPIAN TUBES

促性腺激素对人类输卵管的直接调节

• 批准号: 2204842
• 负责人: Ch V RAO
• 金额: $ 18.68万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2204842
• 关键词: antisense nucleic acid; biological signal transduction; cell cycle; chorionic gonadotropin; epidermal growth factor; estradiol; fallopian tubes; hormone regulation /control mechanism; human tissue; immunocytochemistry; luteinizing hormone; mucosa; northern blottings; nuclear runoff assay; progesterone; protein biosynthesis; radioimmunoassay; receptor expression; secretion; steroid hormone receptor; tissue /cell culture; transfection /expression vector; transforming growth factors; western blottings

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.

人类输卵管，以前从未被认为是一种 hCG/LH调节的直接靶点，表达hCG及其受体基因。 这些基因的表达依赖于组织的解剖区域。 管和妇女的生殖状态。输卵管粘膜， 细胞分裂并在大分子合成和分泌中具有活性， 比其他输卵管细胞层表达更多。输卵管组织孵育 与高纯度的hCG，导致剂量和时间依赖性增加， 具有催化活性的5-脂氧合酶、环氧合酶（考克斯）-1和考克斯-2 输卵管粘膜酶。这些发现表明，hCG和LH可以 独立于卵巢类固醇激素调节输卵管粘膜功能。 然而，这些激素和生长之间可能存在相互作用 管的整体调节的因素。目前的补助金申请 建议调查：1）外源性和内源性hCG的作用， 其受体参与粘膜细胞分裂和大分子合成， 输卵管hCG及其受体是否受卵巢激素的调节 类固醇激素、生长因子和hCG/LH; 3）什么样的信号机制 和介质参与hCG的行动和4）最终是否卵巢 类固醇激素和生长因子可以模拟和/或改变hCG的作用。 将检测hCG和hLH的功能等效性，因为这两种药物 激素是结构和功能上的同系物， 受体。仅使用分泌期的输卵管粘膜， 大量共表达hCG及其受体， 分泌期高于其他生殖期。 这些 反义cDNA表达技术将有助于研究， 其他分子生物学、细胞生物学和生物化学技术。的 这一建议的总体目标是促进我们目前的理解， hCG及其受体在输卵管中的作用和调节， 将输卵管功能的所有潜在调节因子放置在适当的位置， perspective.这些知识可以进一步刺激对hCG/LH的研究 输卵管功能的调节，因为它可能与许多早期事件有关。 怀孕、体外受精、宫外孕和盆腔 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， 输卵管功能障碍足够数量的绝经前输卵管组织 接受输卵管结扎术的妇女，包括少数民族，或 子宫切除术将是可行的。这些研究此前从未 在人类或其他物种的输卵管或子宫上进行。