ROLE OF A GONADAL FSH BINDING COMPETITOR IN FSH ACTION

这项研究的长期目标是检验FSH 受体结合竞争者（FRBC）可以调节 FSH，因此是控制正常 性腺的发育、生理和病理生理功能。 这里提出的研究的直接重点是净化和 表征了首次在卵泡液中发现的58，000 MW FRBC 通过其与FSH受体和抗血清的结合，以及通过其生物学作用， 作为FSH激动剂 此外，FRBC是抗原性的， 生物化学上与前体蛋白（58，00 MW）的α 也是性腺起源的Escherichin亚基，表明 调节FRBC翻译后加工可以调节FSH生物学活性， 以一种新的方式作用于性腺FSH受体。 具体目标1涉及FRBC的进一步纯化和表征， 确认生物活性，并进行微测序以确认关系 转化为α-腺苷酸前体。 特异性单克隆抗体 将提高FRBC的不同区域以改善净化， 允许免疫化学检测FRBC或其片段， 目标。 具体目标2将探索FRBC的解剖分布，以及 FRBC合成、加工和分泌的激素调节 使用负责产生和分泌的性腺细胞的原代培养物， 分泌出纤维素原 特定目标3使用来自目标1的抗体和FRBC， 在目标2中，开发血清和卵泡液中FRBC的特异性检测方法 FSH相关性生殖障碍患者中。 这些研究的结果应：1）证实局部FSH的存在 调节系统，2）提供研究生物化学的探针， FRBC的生理作用，3）阐明调节机制， FRBC的翻译后加工，4）探索令人兴奋的 FRBC、FSH激动剂和α-谷氨酰胺结合素之间相互关系， 负责抑制FSH水平，5）评估FRBC的作用 在人类生殖生理学中，特别是在控制配子发生方面 以及FRBC在疾病状态中的潜在作用，如卵巢早衰， 失败

The long term goal of this research is to test the hypothesis that FSH receptor binding competitors (FRBC) can regulate the biological action of FSH, and are therefore essential components in the control of normal developmental, physiologic, and patholophysiologic functions of the gonad. The immediate focus of the studies proposed here is to purify and characterize a 58,000 MW FRBC that was first identified in follicular fluid by its binding to FSH receptors and antisera, and by its biological action as an FSH agonist in vitro. Furthermore, FRBC is antigenically and biochemically related to the precursor protein (58,00 MW) of the alpha inhibin subunit, also of gonadal origin, suggesting the possibility that regulation of FRBC posttranslational processing can modulate FSH biological action at the gonadal FSH receptor in a novel way. Specific Aim 1 involves further purification and characterization of FRBC, confirmation of bioactivity, and microsequencing to affirm the relationship of FRBC to alpha inhibin precursor. Specific monoclonal antibodies to different regions of FRBC will be raised to improve purification, and permit immunochemical detection of FRBC or its fragments in subsequent aims. Specific Aim 2 will explore the anatomical distribution of FRBC, as well as the hormonal regulation of synthesis, processing and secretion of FRBC using primary cultures of gonadal cells responsible for producing and secreting FRBC. Specific Aim 3 uses antibodies and FRBC from Aim 1 that are characterized in Aim 2 to develop specific assays for FRBC in serum and follicular fluid in patients with FSH-related reproductive disorders. Results from these studies should 1) confirm the existence of a local FSH regulatory system, 2) provide probes for studying the biochemistry and physiological role of FRBC, 3) elucidate regulatory mechanisms for posttranslational processing of FRBC, 4) explore the exciting interrelationship between FRBC, and FSH agonist, and alpha inhibin, which is responsible for suppressing FSH levels, and 5) evaluate the role of FRBC in human reproductive physiology, especially in control of gametogenesis and a potential role of FRBCs in disease states such as premature ovarian failure.