These studies should also be applicable to the biosynthesis of all the other neuronal peptide hormones. 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. 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. Pulse-chase experiments have definitely proven that beta-endorphin is a maturation product of a large precursor also containing ACTH and MSH. Finally, the addition of ACTH completed a putative multipotent precursor model that has been recently named pro-opiomelanocortin. 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.
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 demonstration of specific brain opiate receptors led to the hypothesis of the existence of endogenous opiate ligands which could act as neurotransmittors. The discovery of endorphins brought together two fields of research that were not related: the opiates and the so-called pituitary lipotropic hormones. This concept was simultaneously proposed for proinsulin and applied later to other polypeptide hormones. 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.
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