CHEMISTRY AND BIOLOGY OF HUMAN AND OTHER GONADOTROPINS

人类和其他促性腺激素的化学和生物学

• 批准号: 3310978
• 负责人: OM P BAHL
• 金额: $ 22.15万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3310978
• 关键词: acetylation; affinity chromatography; carbohydrate sequence; chemical group; chemical structure function; chemical synthesis; chorionic gonadotropin; complementary DNA; cyclic AMP; disulfide bond; female antifertility drug; fertility immunology; follicle stimulating hormone; glycosylation; glycosyltransferase; gonadotropins; hormone receptor; human pregnant subject; human subject; immunofluorescence technique; laboratory mouse; laboratory rabbit; laboratory rat; luteinizing hormone; molecular cloning; neoplasm /cancer diagnosis; nucleic acid probes; phosphorylation; placenta; protein sequence; radioimmunoassay; spermicide; steroid hormone biosynthesis; thin layer chromatography; vaccines

The major thrust of the proposed studies is essentially two fold: (1) the isolation and characterization of the hCG/hLH receptor from superovulated rat ovaries and (2) the structure and function relationships in gonadotropins. The studies on hCG/hLH receptor will include (a) partial amino acid sequencing of the receptor subunits by a gas phase sequenator with the objective of using the sequence information to synthesize cDNA probes for the isolation and cloning of the receptor gene, (b) the determination of molecular properties of the receptor such as phosphorylation, glycosylation and acylation, and (c) production of monoclonal and polyclonal antibodies against the receptor. Structure and function studies will primarily focus on the role of carbohydrates in the function of gonadotropins. The cellular and molecular mechanisms of carbohydrate action in the hormonal signal transduction from hormone-receptor complex to the adenylate cyclase system and to the subsequent biological events will be studied. The effect of carbohydrate of the ligand on the induction of specific conformational change in the receptor, its desensitization and internalization will be investigated. The role of carbohydrate in eCG will also be studied and the effect of its removal on both its LH and FSH activities will be determined. The hCG specific antigenic site in DS5-hCG-Beta, a specific antigen obtained by the controlled reduction and alkylation of hCG-Beta, will be identified. This will be further confirmed by using synthetic peptide representing the hCG specific antigenic site and studying the inhibition of binding of DS5-hCG-Beta to its antibody by the peptide. Finally, the heterogeneity of carbohydrates in hCG, oLH and disease state hCG will be investigated by the newly developed thin layer chromatographic system. These basic studies on the receptor and hormone function would help in developing newer approaches to fertility regulation. Furthermore, the monoclonal antibodies to hCG-Alpha and hCG-Beta have potential in cancer diagnosis.

拟议研究的主旨主要有两方面：(1) 超数排卵人绒毛膜促性腺激素/促黄体生成素受体的分离与鉴定 (2)大鼠卵巢的结构和功能关系 促性腺激素。人绒毛膜促性腺激素/促黄体生成素受体的研究将包括(A)部分 用气相测序仪测定受体亚基的氨基酸序列 目的是利用序列信息合成cDNAs 用于分离和克隆受体基因的探针，(B) 受体分子性质的测定，如 磷酸化、糖基化和酰化，以及(C)生产 抗该受体的单抗和多克隆抗体。结构和 功能研究将主要集中在碳水化合物在 促性腺激素的功能。细胞和分子机制的研究进展 糖类在内分泌信号转导中的作用 激素受体复合体对腺苷酸环化酶系统和 后续的生物事件将被研究。碳水化合物的作用 配体在诱导细胞内特异性构象变化中的作用 受体，它的脱敏和内化将被研究。 碳水化合物在心电图中的作用也将被研究，以及它的影响 对其促黄体生成素和促卵泡刺激素活性的去除将被确定。人绒毛膜促性腺激素 在ds5-hCG-Beta中的特异性抗原部位，是由 将确定hCG-Beta的受控还原和烷基化。这 将通过使用代表hCG的合成肽来进一步确认 特异性抗原结合位点及其结合抑制作用的研究 Ds5-hCG-Beta通过多肽与其抗体结合。最后，数据的异构性 HCG、olh和疾病状态hCG中的碳水化合物将由 新开发的薄层色谱系统。这些基础研究是关于 受体和激素的功能将有助于开发新的方法 生育调控。此外，针对该病毒的单抗 人绒毛膜促性腺激素α和人绒毛膜促性腺激素β在肿瘤诊断中具有潜在的应用价值。