EXTRAPITUITARY ACTIONS OF LHRH AGONISTS

这项提议的一个主要目的是分离、表征和合成一种 睾丸和卵巢促性腺激素释放激素样物质(S)可能起作用 在性腺功能的细胞内调节中。隔离 足够进行氨基酸测序的数量将在 取自大鼠、公牛和人类睾丸的材料。当氨基酸 纯材料的序列是已知的，它将被合成和 合成肽及其类似物将在体内和体外进行检测 不同物种的生物活性。还将确定这些是否 物质因物种而异。牛半乳中的一种类LHRH物质 血浆和卵泡液也将被研究。这将是 使用各种提取方法、解聚和还原完成 对类LHRH物质进行脱盐、亲和层析和反相 相和/或离子交换高效液相色谱法。我们认为性腺LHRH样蛋白 物质是性腺LHRH受体的内源性配体。是这样的 在大鼠的睾丸中发现了受体，而在小鼠的睾丸中没有。 和人类。未能证明LHRH受体的存在 小鼠和人性腺和LHRH激动剂的明显失败 小鼠的抗生殖作用可能与此有关。我们建议 促性腺激素释放激素激动剂、促性腺激素和性激素的相互作用 有必要对这些发现进行进一步的调查。占用 睾丸LHRH受体通过内源性配体可解释 在老鼠和人类身上明显缺乏这些受体。这也是可能的 这些非老鼠物种的睾丸含有类似LHRH的物质。我们 将首先检查小鼠以确定LHRH激动剂是否直接抑制 他们的性腺功能。这些实验将被设计成将 促性腺激素释放激素激动剂、促性腺激素和/或性别之间可能的相互作用 类固醇。睾丸、腹侧前列腺和精液的重量 囊泡、睾丸形态、睾丸LHRH受体含量，以及 在体内和体外检测睾酮的产生 LHRH激动剂治疗。体外实验：用培养的睾丸或 来自不同物种的卵巢组织也将被进行。

A major aim of this proposal is to isolate, characterize and synthesize a testicular and ovarian LHRH-like substance(s) which probably plays a role in the intracellular regulation of gonadal functions. Isolation of quantities sufficient for amino acid sequencing will be conducted on material obtained from rat, bull and human testes. When the amino acid sequence of the pure material is known, it will be synthesized and the synthetic peptide and its analogs will be examined for in vivo and in vitro bioactivity in various species. It will also be determined if these substances are species specific. A LHRH-like substance in bovine semial plasma and follicular fluid will also be studied. This will be accomplished using various extraction methods, disaggregation and reduction of the LHRH-like substance, desalting, afficity chromatography, and reverse phase and/or ion exchange HPLC. We propose that a gonadal LHRH-like substance is the endogenous ligand for gonadal LHRH receptors. Such receptors have been found in the testes of rats, but not in those of mice and humans. Failures to demonstrate the presence of LHRH receptors in mouse and human gonads and the apparent failure of LHRH agonists to have antireproductive actions in mice might be related. We suggest that interactions between LHRH agonists, gonadotropins and sex steroids necessitate further investigation of these findings. Occupation of testicular LHRH receptors by endogenous ligand could account for the apparent lack of these receptors in mice and humans. It is also possible that the testes of these non-rat species contain LHRH-like material. We will first examine mice to determine if LHRH agonists directly suppress their gonadal function. These experiments will be designed to minimize possible interactions between LHRH agonists, gonadotropins and/or sex steroids. The weights of the testes, ventral prostate and seminal vesicles, testicular morphology, testicular LHRH receptor content, and in vivo and in vitro testosterone production with be examined during and after LHRH agonist treatment. In vitro experiments using cultured testicular or ovarian tissue from different species will also be conducted.