CELLULAR AND MOLECULAR MECHANISMS MEDIATING PEPTIDE HORMONE ACTION

在早期的研究中，我们提供的数据包括内皮素，一种新的 最初在内皮细胞中发现的肽家族， 控制LHRH释放。 几条证据表明， 内皮素参与生殖的控制。的影响 所述肽在下丘脑水平通过调节 LHRH的释放，以及通过增强 LH的分泌。我们的研究，利用下丘脑外植体和 释放LHRH的神经元细胞系（GT 1细胞）已经显示， 内皮素-3（ET-3）刺激LHRH分泌，前列腺素E2 是这些效应中可能的细胞内介质。 许多肽能的 胺能系统似乎调节LHRH的释放。 然而，在这方面， 只有少数似乎是积极的内源性控制， 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，必须证明， 内源性物质参与特定的生理现象。 在过去一年，我们致力发展 特异性羊抗ET-3血清，以便使用被动免疫 范式，我们可以评估内源性的相对参与 内皮素在生殖中的作用 在过去的一年里，我们获得了两个 高效价抗ET-3血清可用于被动免疫 问题研究 正在进行的实验正在评估 静脉注射这些抗体后，以评估其适用性 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.