The Posttranslational Processing of β‐Endorphin in Human Hypothalamus

β‐Endorphin is posttranslationally processed to six derivatives, which, although structurally similar, produce distinctly different biological effects. β‐Endorphin 1–31 is a potent opioid receptor agonist, but β‐endorphin 1–27 exhibits antagonist properties, and β‐endorphin 1–26 and the α‐ N ‐ acetyl derivatives of all three peptides lack opioid receptor activity. In the present study, we identified the β‐endorphin peptides synthesized in human hypothalamus using cation exchange HPLC. First, we tested whether postmortem changes occur by storing rat hypothalami at 4°C. This demonstrated that relative amounts of the six β‐endorphin forms did not change for up to 24 h, although total β‐endorphin immunoreactivity significantly declined after 6 h. HPLC analysis of human hypothalami revealed that β‐endorphin 1–31 was the principal form, constituting 58.4 ± 5.4% of total immunoreactivity. Substantial amounts of β‐endorphin 1–27 (13.4 ± 1.2%) and β‐endorphin 1–26 (13.1 ± 1.6%) were also present, but α‐ N ‐acetylated forms were quantitatively minor, each comprising ∼5% of total β‐endorphin. A similar processing pattern occurred in preoptic and supra‐ chiasmatic areas of the hypothalamus. These results show that, despite differences in primary sequence, β‐endorphin is processed similarly in both rat and human hypothalamus. Opiate‐active β‐endorphin 1–31 is the principal form in both species.