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. 1970 Mar;65(3):745–752. doi: 10.1073/pnas.65.3.745

ACTH Receptors in the Adrenal: Specific Binding of ACTH-125I and Its Relation to Adenyl Cyclase

Robert J Lefkowitz 1,2, Jesse Roth 1,2, William Pricer 1,2, Ira Pastan 1,2
PMCID: PMC282969  PMID: 4315615

Abstract

Pure monoiodo ACTH-125I was prepared that was biologically active and free of unlabeled ACTH. Extracts of adrenal cortex that contained ACTH-sensitive adenyl cyclase, bound ACTH-125I; extracts that lacked the ACTH-sensitive cyclase did not bind ACTH-125I. Unlabeled ACTH inhibited the binding of ACTH-125I. Five ACTH derivatives which varied widely in biological activity were tested. All inhibited the binding of ACTH-125I in direct proportion to their biological activity. Albumin, insulin, and four unrelated iodinated hormones were inert. The addition of excess hormone or acetic acid produced rapid dissociation of bound ACTH-125I. This study demonstrates directly the binding of ACTH to its biologically significant site.

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Selected References

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

  1. BIRMINGHAM M. K., KURLENTS E. Inactivation of ACTH by isolated rat adrenals and inhibition of corticoid formation by adrenocortical hormones. Endocrinology. 1958 Jan;62(1):47–60. doi: 10.1210/endo-62-1-47. [DOI] [PubMed] [Google Scholar]
  2. Bernstein R. S., Wilchek M., Edelhoch H. Structural studies on polypeptide hormones. II. Polarization of fluorescence. J Biol Chem. 1969 Aug 25;244(16):4398–4405. [PubMed] [Google Scholar]
  3. Berson S. A., Yalow R. S. Radioimmunoassay of ACTH in plasma. J Clin Invest. 1968 Dec;47(12):2725–2751. doi: 10.1172/JCI105955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Birnbaumer L., Rodbell M. Adenyl cyclase in fat cells. II. Hormone receptors. J Biol Chem. 1969 Jul 10;244(13):3477–3482. [PubMed] [Google Scholar]
  5. DIXON H. B. Treatment of corticotrophin with periodate and borohydride. Biochem J. 1962 Apr;83:91–94. doi: 10.1042/bj0830091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edelhoch H., Lippoldt R. E. Structural studies on polypeptide hormones. I. Fluorescence. J Biol Chem. 1969 Jul 25;244(14):3876–3883. [PubMed] [Google Scholar]
  7. Edelhoch H. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry. 1967 Jul;6(7):1948–1954. doi: 10.1021/bi00859a010. [DOI] [PubMed] [Google Scholar]
  8. Edelman I. S., Fimognari G. M. On the biochemical mechanism of action of aldosterone. Recent Prog Horm Res. 1968;24:1–44. doi: 10.1016/b978-1-4831-9827-9.50007-1. [DOI] [PubMed] [Google Scholar]
  9. Edelman P. M., Schwartz I. L. Subcellular distribution of I131-insulin in striated muscle. Am J Med. 1966 May;40(5):695–708. doi: 10.1016/0002-9343(66)90150-1. [DOI] [PubMed] [Google Scholar]
  10. Fong C. T., Silver L., Christman D. R., Schwartz I. L. ON THE MECHANISM OF ACTION OF THE ANTIDIURETIC HORMONE (VASOPRESSIN). Proc Natl Acad Sci U S A. 1960 Oct;46(10):1273–1277. doi: 10.1073/pnas.46.10.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HAYNES R. C., Jr The activation of adrenal phosphorylase by the adrenocorticotropic hormone. J Biol Chem. 1958 Nov;233(5):1220–1222. [PubMed] [Google Scholar]
  12. 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]
  13. IZZO J. L., RONCONE A., IZZO M. J., BALE W. F. RELATIONSHIP BETWEEN DEGREE OF IODINATION OF INSULIN AND ITS BIOLOGICAL, ELECTROPHORETIC, AND IMMUNOCHEMICAL PROPERTIES. J Biol Chem. 1964 Nov;239:3749–3754. [PubMed] [Google Scholar]
  14. Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
  15. Lunenfeld B., Eshkol A. Immunology of human chorionic gonadotropin (HCG). Vitam Horm. 1967;25:137–190. doi: 10.1016/s0083-6729(08)60036-9. [DOI] [PubMed] [Google Scholar]
  16. Pastan I., Roth J., Macchia V. Binding of hormone to tissue: the first step in polypeptide hormone action. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1802–1809. doi: 10.1073/pnas.56.6.1802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. REINHARDT W. O., GESHWIND I. I., PORATH J. O., LI C. H. Significance of intermedin activity in adrenocorticotropic hormone preparation. Proc Soc Exp Biol Med. 1952 Jul;80(3):439–442. doi: 10.3181/00379727-80-19650. [DOI] [PubMed] [Google Scholar]
  18. Rodbell M. Metabolism of isolated fat cells. V. Preparation of "ghosts" and their properties; adenyl cyclase and other enzymes. J Biol Chem. 1967 Dec 25;242(24):5744–5750. [PubMed] [Google Scholar]
  19. SONENBERG M., KESTON A. S., MONEY W. L. Tracer studies with labeled preparations of anterior pituitary hormones: ACTH. J Clin Endocrinol Metab. 1950 Jul;10(7):809–809. [PubMed] [Google Scholar]
  20. Schimmer B. P., Ueda K., Sato G. H. Site of action of adrenocorticotropic hormone (ACTH) in adrenal cell cultures. Biochem Biophys Res Commun. 1968 Sep 6;32(5):806–810. doi: 10.1016/0006-291x(68)90312-4. [DOI] [PubMed] [Google Scholar]
  21. Taunton O. D., Roth J., Pastan I. Studies on the adrenocorticotropic hormone-activated adenyl cyclase of a functional adrenal tumor. J Biol Chem. 1969 Jan 25;244(2):247–253. [PubMed] [Google Scholar]
  22. Yasumura Y., Buonassisi V., Sato G. Clonal analysis of differentiated function in animal cell cultures. I. Possible correlated maintenance of differentiated function and the diploid karyotype. Cancer Res. 1966 Mar;26(3):529–535. [PubMed] [Google Scholar]

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