THIS REVIEW will deal with the biosynthesis of many of the members of the ACTH/lipotropin (LPH) family of peptides (Fig. 1). Peptides in this family fall into two groups: peptides related to ACTH include α-melanotropin (αMSH) and corticotropin-like intermediate lobe peptide (CLIP); peptides related to βLPH include γLPH, βMSH, and β-endorphin. In several species ACTH and βLPH each contain an identical heptapeptide segment located in the region of the molecule that is responsible for melanotropic bioactivity (1, 2). In this review we have taken a somewhat historical approach, and will therefore begin with a discussion of the biosynthesis of ACTH and the characterization of biosynthetic precursors to ACTH. When this work began, βLPH, γLPH, and βMSH were well-characterized pituitary peptides, but the opioid peptides (and β-endorphin in particular) had not yet been identified (3–5). Studies on the biosynthesis of ACTH were heavily influenced by prior work defining the biosynthetic pathways for insulin and para...

Structure and Biosynthesis of Pro-Adrenocorticotropin/Endorphin and Related Peptides*

The opiomelanotropinergic neuronal and endocrine systems.

Publisher Summary This chapter discusses the organization, characteristics, release, and modulation of hypophyseal and other endocrinologically relevant pools of opioid peptides and their possible target sites and functions. The nature and role of opioid mechanisms in the control of the endocrine secretion of various tissues are considered in the chapter. Many conditions—for example, stress, nutritional status, degree of hydration, and phase of circadian or estrus cyclicity—have biochemically been shown to be (1) associated with alterations in the activity of endocrine-like opioid systems and (2) related to opioid-mediated changes in behavioral, physiological, and endocrinological measures. It is the unification of these complementary sources of information and the assignation of particular functions to particular endocrine-like pools of opioids that are of importance. The chapter also discusses a particular aspect of the function of opioid mechanisms, including endocrine-like opioid peptide systems—that is, of their modulation of the secretion of hormones into the systemic circulation. The ability of opioids to modify these endocrine parameters is among their most striking properties and, especially in the case of antagonists, no less impressive than their role in antinociceptive processes. There are multifarious sites of attack and mechanisms of action by which opioid mechanisms may modulate endocrine secretion. Similarly, a diversity of opioid ligands and receptor types is implicated in particular cases. An elucidation of the roles of individual ligands and receptor types at specific loci and their relationships to other control systems under specific conditions has not been achieved.

The endocrinology of the opioids.

Intranasal administration of oxytocin: behavioral and clinical effects, a review.

Increase in potencies of opioid peptides after peptidase inhibition.

β-Endorphin (β-LPH61–91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller β-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations1. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of γ-endorphin (β-LPH61–77) by removing the N-terminal amino acid yielded des-tyrosine-γ-endorphin (β-LPH62–77, dTγE) which had greater behavioural activity than γ-endorphin2,3. The CNS effects of dTγE resembled those of neuroleptic drugs in several test systems, α-Endorphin (β-LPH61–76) exerted effects opposite to those of dTγE and in some aspects its activity was comparable to that of psychostimulant drugs4. This opposition of effects suggests that a balance between γ- and α-type endorphins is involved in the control of brain function5. We report here that either γ-endorphin and dTγE or α-endorphin and des-tyrosine-α-endorphin (β-LPH62–769 dTαE) can be formed preferentially from β-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.

Selective conversion of β-endorphin into peptides related to γ- and α-endorphin

Combination of high pressure liquid chromatography and radioimmunoassay is a powerful tool for the specific and quantitative determination of endorphins and related peptides

J.G. Loeber

Papers

Selective conversion of β-endorphin into peptides related to γ- and α-endorphin

Combination of high pressure liquid chromatography and radioimmunoassay is a powerful tool for the specific and quantitative determination of endorphins and related peptides

α-Endorphin, γ-endorphin and their Des tyrosine fragments in rat pituitary and brain tissue

Schizophrenia and degradation of endorphins in cerebrospinal fluid

Biotransformation of endorphins by a synaptosomal plasma membrane preparation of rat brain and by human serum