CHEMISTRY AND BIOLOGY OF HUMAN AND OTHER GONADOTROPINS

拟议研究的主要目的基本上有两个方面：（1） 超数排卵小鼠hCG/hLH受体的分离和鉴定 大鼠卵巢的结构和功能关系 促性腺激素 对hCG/hLH受体的研究将包括（a）部分 通过气相测序仪对受体亚基进行氨基酸测序 目的是利用序列信息合成cDNA 用于分离和克隆受体基因的探针，（B） 确定受体的分子特性，例如 磷酸化、糖基化和酰化，和（c）产生 针对受体的单克隆和多克隆抗体。 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。 的细胞分子机制 碳水化合物在激素信号转导中的作用， 腺苷酸环化酶系统和腺苷酸受体复合物 将研究随后的生物学事件。 碳水化合物的作用 的配体对诱导特定的构象变化， 受体，其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， 将测定其LH和FSH活性的去除。 的hCG DS5-hCG-β中的特异性抗原位点，DS5-hCG-β是通过 将鉴定hCG-β的受控还原和烷基化。 这 将通过使用代表hCG的合成肽进一步证实 特异性抗原位点，并研究结合抑制 DS5-hCG-β通过肽段与其抗体结合。 最后， 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 受体和激素功能将有助于开发新的方法， 生育调节。 此外，针对 hCG-α和hCG-β在癌症诊断中具有潜力。

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.