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. 1972 Jan;51(1):141–148. doi: 10.1172/JCI106784

Biosynthesis of Vasopressin In Vitro and Ultrastructure of a Bronchogenic Carcinoma

PATIENT WITH THE SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE

Jack M George 1,2, Charles C Capen 1,2, Audra S Phillips 1,2
PMCID: PMC332939  PMID: 5007044

Abstract

Tumors from patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been found to contain large amounts of the antidiuretic hormone vasopressin. A lung tumor from a patient with hyponatremia most likely due to SIADH was removed at surgery and found to contain 23.5 mU vasopressin/g wet weight by radioimmunoassay Slices of this tumor were incubated with phenylalanine-3H. Arginine vasopressin-3H was purified from the incubate by Sephadex G-25 column chromatography in two different systems, performic acid oxidation, and gradient elution column chromatography with diethylaminoethyl Sephadex. As oxidation of vasopressin results in drastic conformational change with breaking of the ring of the cyclic polypeptide and addition of two cysteic acid residues per molecule, the radioactive material which eluted coincident with vasopressin both before and after this procedure was considered to be arginine vasopressin-3H. To our knowledge this is the first demonstration of in vitro biosynthesis of vasopressin by a tumor from a patient with SIADH.

Ultrastructurally, the bronchogenic carcinoma was composed of small undifferentiated and granulated cells. The granulated neoplastic cells had well developed organelles (endoplasmic reticulum, free ribosomes) concerned with protein synthesis. Secretion granules present in the tumor cells were small, surrounded by a limiting membrane, and resembled those reported in polypeptide hormone-secreting cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AMATRUDA T. T., Jr, MULROW P. J., GALLAGHER J. C., SAWYER W. H. CARCINOMA OF THE LUNG WITH INAPPROPRIATE ANTIDIURESIS. DEMONSTRATION OF ANTIDIURETIC-HORMONE-LIKE ACTIVITY IN TUMOR EXTRACT. N Engl J Med. 1963 Sep 12;269:544–549. doi: 10.1056/NEJM196309122691102. [DOI] [PubMed] [Google Scholar]
  2. BOWER B. F., MASON D. M., FORSHAM P. H. BRONCHOGENIC CARCINOMA WITH INAPPROPRIATE ANTIDIURETIC ACTIVITY IN PLASMA AND TUMOR. N Engl J Med. 1964 Oct 29;271:934–938. doi: 10.1056/NEJM196410292711804. [DOI] [PubMed] [Google Scholar]
  3. Bauer W. C., Teitelbaum S. L. Thyrocalcitonin activity of particulate fractions of the thyroid gland. Lab Invest. 1966 Jan;15(1 Pt 2):323–329. [PubMed] [Google Scholar]
  4. Bensch K. G., Corrin B., Pariente R., Spencer H. Oat-cell carcinoma of the lung. Its origin and relationship to bronchial carcinoid. Cancer. 1968 Dec;22(6):1163–1172. doi: 10.1002/1097-0142(196811)22:6<1163::aid-cncr2820220612>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  5. Bergland R. M., Torack R. M. An ultrastructural study of follicular cells in the human anterior pituitary. Am J Pathol. 1969 Nov;57(2):273–297. [PMC free article] [PubMed] [Google Scholar]
  6. Coalson J. J., Mohr J. A., Pirtle J. K., Dee A. L., Rhoades E. R. Electron microscopy of neoplasms in the lung with special emphasis on the alveolar cell carcinoma. Am Rev Respir Dis. 1970 Feb;101(2):181–197. doi: 10.1164/arrd.1970.101.2.181. [DOI] [PubMed] [Google Scholar]
  7. GOODFRIEND T. L., LEVINE L., FASMAN G. D. ANTIBODIES TO BRADYKININ AND ANGIOTENSIN: A USE OF CARBODIIMIDES IN IMMUNOLOGY. Science. 1964 Jun 12;144(3624):1344–1346. doi: 10.1126/science.144.3624.1344. [DOI] [PubMed] [Google Scholar]
  8. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  9. HYMER W. C., McSHAN W. H. Isolation of rat pituitary granules and the study of their biochemical properties and hormonal activities. J Cell Biol. 1963 Apr;17:67–86. doi: 10.1083/jcb.17.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hollenberg M. D., Hope D. B. The isolation of the native hormone-binding proteins from bovine pituitary posterior lobes. Crystallization of neurophysin-I and-II as complexes with [8-arginine]-vasopressin. Biochem J. 1968 Jan;106(2):557–564. doi: 10.1042/bj1060557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kay S., Willson M. A. Ultrastructural studies of an ACTH-secreting thymic tumor. Cancer. 1970 Aug;26(2):445–452. doi: 10.1002/1097-0142(197008)26:2<445::aid-cncr2820260228>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  12. Lacy P. E. The pancreatic beta cell. Structure and function. N Engl J Med. 1967 Jan 26;276(4):187–195. doi: 10.1056/NEJM196701262760401. [DOI] [PubMed] [Google Scholar]
  13. Lipscomb H. S., Wilson C., Retiene K., Matsen F., Ward D. N. The syndrome of inappropriate secretion of antidiuretic hormone: a case report and characterization of an antidiuretic hormone-like material isolated from an oat cell carcinoma of the lung. Cancer Res. 1968 Feb;28(2):378–383. [PubMed] [Google Scholar]
  14. Mallory A., Smith G. H., Taylor K. W. The incorporation of tritium-labelled amino acids into insulins in rat pancreas in vitro. Biochem J. 1964 Jun;91(3):484–491. doi: 10.1042/bj0910484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marks L. J., Berde B., Klein L. A., Roth J., Goonan S. R., Blumen D., Nabseth D. C. Inappropriate vasopressin secretion and carcinoma of the pancreas. Am J Med. 1968 Dec;45(6):967–974. doi: 10.1016/0002-9343(68)90196-4. [DOI] [PubMed] [Google Scholar]
  16. Obiditsch-Mayer I., Breitfellner G. Electron microscopy in cancer of the lung. Cancer. 1968 May;21(5):945–951. doi: 10.1002/1097-0142(196805)21:5<945::aid-cncr2820210519>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  17. POPENOE E. A., DU VIGNEAUD V. Degradative studies on vasopressin and performic acid-oxidized vasopressin. J Biol Chem. 1953 Nov;205(1):133–143. [PubMed] [Google Scholar]
  18. Razzuk M. A., Race G. J., Lynn J. A., Martin J. A., Urschel H. C., Jr, Paulson D. L. Observations on ultrastructural morphology of bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1970 Apr;59(4):581–587. [PubMed] [Google Scholar]
  19. Razzuk M. A., Race G. J., Urschel H. C., Jr, Martin J. A., McNamara J. J., Paulson D. L. Mitochondrial peculiarities in bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1970 Aug;60(2):291–296. [PubMed] [Google Scholar]
  20. Roth J., Glick S. M., Klein L. A., Petersen M. J. Specific antibody to vasopressin in man. J Clin Endocrinol Metab. 1966 Jun;26(6):671–675. doi: 10.1210/jcem-26-6-671. [DOI] [PubMed] [Google Scholar]
  21. SCHWARTZ W. B., BENNETT W., CURELOP S., BARTTER F. C. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med. 1957 Oct;23(4):529–542. doi: 10.1016/0002-9343(57)90224-3. [DOI] [PubMed] [Google Scholar]
  22. Sawyer W. H. Pharmacological characteristics of the antidiuretic principle in a bronchogenic carcinoma from a patient with hyponatremia. J Clin Endocrinol Metab. 1967 Oct;27(10):1497–1499. doi: 10.1210/jcem-27-10-1497. [DOI] [PubMed] [Google Scholar]
  23. Stoebner P., Cussac Y., Porte A., Le Gal Y. Ultrastructure of anaplastic bronchial carcinomas. Cancer. 1967 Feb;20(2):286–294. doi: 10.1002/1097-0142(1967)20:2<286::aid-cncr2820200216>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  24. TAKABATAKE Y., SACHS H. VASOPRESSIN BIOSYNTHESIS. 3. IN VITRO STUDIES. Endocrinology. 1964 Dec;75:934–942. doi: 10.1210/endo-75-6-934. [DOI] [PubMed] [Google Scholar]
  25. Utiger R. D. Inappropriate antidiuresis and carcinoma of the lung: detection of arginine vasopressin in tumor extracts by immunoassay. J Clin Endocrinol Metab. 1966 Sep;26(9):970–974. doi: 10.1210/jcem-26-9-970. [DOI] [PubMed] [Google Scholar]
  26. Vorherr H., Massry S. G., Utiger R. D., Kleeman C. R. Antidiuretic principle in malignant tumor extracts from patients with inappropriate ADH syndrome. J Clin Endocrinol Metab. 1968 Feb;28(2):162–168. doi: 10.1210/jcem-28-2-162. [DOI] [PubMed] [Google Scholar]
  27. Whitelaw A. G. Ultrastructure of an oat cell carcinoma of the bronchus producing an antidiuretic hormone. Br J Cancer. 1969 Mar;23(1):69–72. doi: 10.1038/bjc.1969.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zambrano D., De Robertis E. The secretory cycle of supraoptic neurons in the rat: a structural-functional correlation. Z Zellforsch Mikrosk Anat. 1966;73(3):414–431. doi: 10.1007/BF00329020. [DOI] [PubMed] [Google Scholar]

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