beta-endorphin and Thymus-Neoplasms

We report a case of a 25-year-old man with Cushing's syndrome due to an ACTH and CRH-producing thymic carcinoid. Immunohistology and radioimmunoassay demonstrated CRH and a lesser amount of ACTH in the resected primary tumor. After a symptom-free period, the tumor recurred and the patient died. Tumor obtained at autopsy contained mainly ACTH and lesser quantities of CRH. We conclude that this thymic carcinoid initially produced mainly CRH and then transformed to secrete mainly ACTH, suggesting that endocrine tumors may change their functional phenotype.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Carcinoid Tumor; Corticotropin-Releasing Hormone; Cushing Syndrome; Humans; Immunohistochemistry; Male; Neoplasm Recurrence, Local; Thymus Neoplasms

An ACTH-producing thymic carcinoid tumour was diagnosed in a 10-year-old girl, 8 years after bilateral adrenalectomy for Cushing's syndrome. The peptides produced by the tumour were characterised thoroughly. High circulating levels of beta-endorphin and other peptides may have contributed to mood and behaviour disturbances.

Topics: ACTH Syndrome, Ectopic; beta-Endorphin; Carcinoid Tumor; Child; Cushing Syndrome; Female; Humans; Paraneoplastic Endocrine Syndromes; Potassium; Thymus Neoplasms

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