Chrétien M, Seidah N G, Scherrer H
Can J Physiol Pharmacol. 1981 May;59(5):413-31.
The knowledge of the amino acid sequence of both beta-lipotropin (beta-LPH) and gamma-LPH was the starting point that led to the hypothesis, considered revolutionary in 1967, that hormonal precursors exist. This concept was simultaneously proposed for proinsulin and applied later to other polypeptide hormones. The discovery of endorphins brought together two fields of research that were not related: the opiates and the so-called pituitary lipotropic hormones. The demonstration of specific brain opiate receptors led to the hypothesis of the existence of endogenous opiate ligands which could act as neurotransmittors. The isolation of such substances in the brain, first named enkephalins, revealed through their amino acid sequence their structural homology with the pituitary lipolytic hormones. The finding of a more potent opioid substance in the pituitary (beta-endorphin) that comprises the last 31 amino acids of beta-LPH shed a new light on the hypothesis proposed earlier which gave to beta-LPH a role as a precursor molecule. Finally, the addition of ACTH completed a putative multipotent precursor model that has been recently named pro-opiomelanocortin. Pulse-chase experiments have definitely proven that beta-endorphin is a maturation product of a large precursor also containing ACTH and MSH. In other studies, many groups have suggested that endorphins play important roles as possible neuromodulators in pain transmission, in analgesia, in tolerance and dependence, as well as on behavior and endocrine regulations, mainly those related to the hypothalamo-pituitary axes. The elucidation of the biosynthetic process or processes of cerebral endorphins (either enkephalins or beta-endorphin) is of primary importance in order ot understand better their biological as well as regulatory functions. These studies should also be applicable to the biosynthesis of all the other neuronal peptide hormones. It is hoped that they will provide new tools for the study of some important central nervous system functions, such as pain and endocrine control and the physiopathology of behavioral diseases.
β-促脂素（β-LPH）和γ-LPH氨基酸序列的知识是提出激素前体存在这一假说的起点，该假说在1967年被认为具有革命性。这一概念同时被应用于胰岛素原，并在后来应用于其他多肽激素。内啡肽的发现将两个不相关的研究领域结合在一起：阿片类药物和所谓的垂体促脂激素。特异性脑阿片受体的证实导致了内源性阿片配体存在的假说，这些配体可作为神经递质发挥作用。在大脑中分离出这类物质，最初命名为脑啡肽，通过其氨基酸序列揭示了它们与垂体脂解激素的结构同源性。在垂体中发现一种更有效的阿片样物质（β-内啡肽），它由β-LPH的最后31个氨基酸组成，这为早期提出的β-LPH作为前体分子的假说提供了新的线索。最后，促肾上腺皮质激素（ACTH）的加入完善了一个假定的多能前体模型，该模型最近被命名为阿黑皮素原。脉冲追踪实验明确证明β-内啡肽是一种大型前体的成熟产物，该前体还含有ACTH和促黑素（MSH）。在其他研究中，许多研究小组表明，内啡肽在疼痛传递、镇痛、耐受性和依赖性以及行为和内分泌调节（主要是与下丘脑-垂体轴相关的调节）中作为可能的神经调节剂发挥重要作用。阐明脑内啡肽（脑啡肽或β-内啡肽）的生物合成过程对于更好地理解它们的生物学和调节功能至关重要。这些研究也应该适用于所有其他神经肽激素的生物合成。希望它们将为研究一些重要的中枢神经系统功能提供新的工具，如疼痛和内分泌控制以及行为疾病的生理病理学。
