CELLULAR AND MOLECULAR MECHANISMS MEDIATING PEPTIDE HORMONE ACTION

在早期的研究中，我们提供了包括内皮素在内的数据，这是一种新的 最初在内皮细胞中发现的多肽家族，在 控制LHRH的释放。有几条证据表明 内皮素参与了生殖的控制。的影响 这些多肽通过调制在下丘脑水平上展示。 促性腺激素释放激素的释放，以及在脑垂体水平，通过促进 促黄体生成素的分泌。我们的研究，利用下丘脑外植体和 释放LHRH的神经细胞系(GT1细胞)，已表明 内皮素-3(ET-3)刺激LHRH分泌和前列腺素E_2 可能是这些效应的细胞内介体。许多多肽能 胺能系统似乎调节LHRH的释放。然而， 只有少数人似乎在内源性地控制着 生理上发生的事件，如青春期和排卵前 促性腺激素激增。为了分配一个生理上重要的 ET-3在生殖事件中的作用，我们必须证明 内源性物质参与特定的生理现象。 在过去的一年里，我们致力于发展一种 使绵羊特异性抗ET-3血清采用被动免疫 范式，我们可以评估内源性的相对参与度 生殖过程中的内皮素。在过去的一年里，我们获得了两个 可用于被动免疫的高效价抗ET-3血清 学习。正在进行的实验正在评估该药的药效学 这些抗体在静脉注射后评估其适用性 阻断内源性ET-3的活性。

In earlier studies we have provided data to include endothelins, a new family of peptides originally discovered in endothelial cells, in the control of LHRH release. Several lines of evidence indicate that endothelins participate in the control of reproduction. The effects of the peptides are exhibited at the level of the hypothalamus by modulating the release of LHRH and, also, at the pituitary level by enhancing the secretion of LH. Our studies, utilizing hypothalamic explants and a neuronal cell line which releases LHRH (GT1 cells), have shown that endothelin-3 (ET-3) stimulates LHRH secretion and that prostaglandin E2 is a possible intracellular mediator in these effects. Many peptidergic and aminergic systems appear to regulate the release of LHRH. However, only a few seem to be active endogenously in the control of physiologically occurring events such as puberty and the preovulatory surge of gonadotropins. In order to assign a physiologically important role for ET-3 in reproductive events, one must demonstrate that the endogenous substance is involved in specific physiological phenomena. During the past year, we have devoted our efforts to developing a specific sheep anti-ET-3 serum so that, using a passive immunization paradigm, we could evaluate the relative participation of endogenous endothelins in reproduction. During the last year, we have obtained two high titer anti-ET-3 sera which could be used in passive immunization studies. Ongoing experiments are evaluating the pharmacodynamics of these antibodies after intravenous injection to assess their suitability for blocking the activity of endogenous ET-3.