beta-endorphin and Thymoma

Beta-endorphin metabolism by CD4+ and CD8+ T cells, and the thymoma cell line, EL4, was investigated. In all three cell types, extracellular beta-endorphin was metabolized exclusively by a secreted, metal-dependent, thiol peptidase. The enzyme activity is expressed constitutively in EL4 cells and following activation of CD4+ and CD8+ T cells with anti-CD3 antibody. The enzyme is not one of the proteinases associated with cytolytic T cells and does not appear to be identical with any previously described beta-endorphin metabolizing enzyme. The enzyme cleaves beta-endorphin at approximately equal rates at either of two sites to yield beta-endorphin(1-17) (which is gamma-endorphin), beta-endorphin(1-18), beta-endorphin(18-31) and beta-endorphin(19-31). Evidence in the literature indicates that these N- and C-terminal peptides which contain, respectively, the opioid and non-opioid receptor binding domains of beta-endorphin, are biologically active. Thus, it is likely that this new T cell peptidase has important immunoregulatory activity.

Topics: Amino Acid Sequence; Animals; beta-Endorphin; Camelus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Endopeptidases; Humans; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Sulfhydryl Compounds; Thymoma; Tumor Cells, Cultured

Topics: Amino Acid Sequence; Animals; beta-Endorphin; Camelus; CD4 Antigens; Chromatography, High Pressure Liquid; Humans; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Peptide Hydrolases; Spectrophotometry, Ultraviolet; T-Lymphocytes; Thymoma; Thyroid Neoplasms; Tumor Cells, Cultured

Release of plasma ACTH- and beta-endorphin (beta-EP)-like immunoreactivity (LI) was studied in vivo in a patient with an ectopic ACTH-producing malignant thymoma. Administration of lysin vasopressin stimulated concomitant release of plasma ACTH- and beta-EP-LI. Administration of cyproheptadine, naloxone, and somatostatin significantly suppressed plasma levels of ACTH- and beta-EP-LI, while saline infusion did not. Gel exclusion chromatography of the plasma extracts revealed that ACTH-LI consisted of two components, large and small molecular weight form, while beta-EP-LI consisted of three components, large molecular weight, beta-lipotropin-, and beta-EP-sized form; each of these components was incompletely suppressed by somatostatin infusion. It is suggested that certain tumors may have acquired aberrant multiple receptors during malignant transformation which may lead to the paradoxical hormone response as demonstrated in this case.

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cyproheptadine; Endorphins; Humans; Lypressin; Male; Naloxone; Paraneoplastic Endocrine Syndromes; Somatostatin; Thymoma; Thymus Neoplasms

The opioid peptide beta-endorphin binds to specific nonopioid binding sites (Mr 72,000) that are present on the surface of thymoma cells. beta-Endorphin is then internalized, apparently via the Mr 72,000 species, and is subsequently found within intracellular, vesicular structures. This process is accompanied by the down-regulation of the Mr 72,000 binding sites. Our findings suggest that beta-endorphin may modulate cellular functions, such as T-lymphocyte proliferation, at intracellular rather than cell surface sites.

Topics: Animals; beta-Endorphin; Cell Line; Endocytosis; Endorphins; Hydrogen-Ion Concentration; Kinetics; Mice; Receptors, Opioid; Thymoma; Thymus Neoplasms

Binding of 125I-labeled camel beta-endorphin (125I-beta C-endorphin) to cells of several mouse thymoma cell lines was examined and was highest to EL4 cells. 125I-beta C-endorphin binding to EL4 cells was temperature-dependent; it was further characterized at 4 degrees C and exhibited saturability, complete reversibility, structural specificity and pH-dependence. 125I-beta C-endorphin binding was not inhibited by the opioid pentapeptides [Leu] enkephalin or [Met] enkephalin (which share common sequences with the N-terminus of beta C-endorphin) or by the N-terminal beta C-endorphin fragments beta C-endorphin (1-16) or beta C-endorphin (1-27). In contrast, binding was inhibited by beta C-endorphin (1-31), indicating that beta C-endorphin binding to EL4 cells was with a C-terminal beta C-endorphin segment. We suggest that binding of beta-endorphin to such nonopioid binding sites may precede its apparent effects on the proliferation of T-lymphocytes (5,6).

Topics: Animals; beta-Endorphin; Cells, Cultured; Endorphins; Hydrogen-Ion Concentration; Mice; Receptors, Opioid; Temperature; Thymoma; Thymus Neoplasms; Time Factors