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. 1981 Jan;67(1):124–133. doi: 10.1172/JCI110004

Simultaneous Assay of Immunoreactive β-Lipotropin, γ-Lipotropin, and β-Endorphin in Plasma of Normal Human Subjects, Patients with ACTH/Lipotropin Hypersecretory Syndromes, and Patients undergoing Chronic Hemodialysis

Xavier Y Bertagna 1, William J Stone 1, Wendell E Nicholson 1, Charles D Mount 1, David N Orth 1
PMCID: PMC371579  PMID: 6256410

Abstract

We have studied the relative concentrations of the human immunoreactive (IR) peptides γ-lipotropin (hγLPH, [1-58]hβLPH), β-lipotropin (hβLPH), and β-endorphin (hβEND, [61-91]hβLPH) using gel exclusion chromatography together with a specific radio-immunoassay (RIA) for hγLPH and a RIA that (because hβEND is the COOH-terminus of the hβLPH molecule) measures both hβEND and hβLPH on an equimolar basis. In normal subjects, basal plasma IR-hγLPH was often undetectable (<12.5 fmol/ml), but ranged up to 21 fmol/ml, and IR-hβEND/hβLPH was 10.8±0.7 fmol/ml; previous studies by others suggest that most of the IR-hβEND/hβLPH was probably hβLPH. Both IR-hγLPH and IR-hβEND/hβLPH were significantly elevated (P < 0.001) in patients undergoing chronic hemodialysis (101.5±12.7 and 23.8±2.0 fmol/ml, respectively). Their IR-hγLPH coeluted with standard hγLPH as a single peak, and IR-hβEND/hβLPH coeluted with hβLPH; no distinct peak of IR-hβEND was observed. In patients with ACTH/LPH hypersecretion due to Addison's disease, Nelson's syndrome, or ectopic ACTH syndrome, IR-hγLPH and IR-hβEND/hβLPH were both elevated, and IR-hβEND/hβLPH eluted as two peaks, one coeluting with hβLPH and the other with hβEND. The molar concentrations of all three peptides were significantly correlated with one another. The lower concentrations of endogenous IR-hβEND observed may be due in part to its apparent shorter plasma half-life, as estimated in an Addison's patient given a cortisol infusion. The biologic significance of these three peptides in circulating blood is still unknown. The increased levels of hβLPH and hγLPH in plasma of patients with chronic renal failure suggest that the kidney may be an important organ for their metabolism.

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Selected References

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  1. Abe K., Nicholson W. E., Liddle G. W., Island D. P., Orth D. N. Radioimmunoassay of beta-MSH in human plasma and tissues. J Clin Invest. 1967 Oct;46(10):1609–1616. doi: 10.1172/JCI105653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abe K., Nicholson W. E., Liddle G. W., Orth D. N., Island D. P. Normal and abnormal regulation of beta-msh in man. J Clin Invest. 1969 Aug;48(8):1580–1585. doi: 10.1172/JCI106123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akil H., Watson S. J., Barchas J. D., Li C. H. B-ETA-Endorphin immunoreactivity in rat and human blood: radioimmunoassay, comparative levels and physiological alterations. Life Sci. 1979 Apr 30;24(18):1659–1665. doi: 10.1016/0024-3205(79)90250-9. [DOI] [PubMed] [Google Scholar]
  4. Bachelot I., Wolfsen A. R., Odell W. D. Pituitary and plasma lipotropins: demonstration of the artificial nature of betaMSH. J Clin Endocrinol Metab. 1977 May;44(5):939–946. doi: 10.1210/jcem-44-5-939. [DOI] [PubMed] [Google Scholar]
  5. Bertagna X. Y., Nicholson W. E., Sorenson G. D., Pettengill O. S., Mount C. D., Orth D. N. Corticotropin, lipotropin, and beta-endorphin production by a human nonpituitary tumor in culture: evidence for a common precursor. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5160–5164. doi: 10.1073/pnas.75.10.5160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bertagna X. Y., Nicholson W. E., Tanaka K., Mount C. D., Sorenson G. D., Pettengill O. S., Orth D. N. Ectopic production of ACTH, lipotropin, and beta-endorphin by human cancer cells. Structurally related tumor markers. Recent Results Cancer Res. 1979;67:16–25. doi: 10.1007/978-3-642-81320-7_3. [DOI] [PubMed] [Google Scholar]
  7. Bertagna X., Donnadieu M., Idatte J. M., Girard F. Dynamics and characterization of plasma immunoreactive beta-melanocyte stimulating hormone in hemodialysis patients: its relationship to ACTH. J Clin Endocrinol Metab. 1977 Dec;45(6):1179–1186. doi: 10.1210/jcem-45-6-1179. [DOI] [PubMed] [Google Scholar]
  8. Bertagna X., Donnadieu M., Seurin D., Binoux M., Girard F. Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins. Acta Endocrinol (Copenh) 1979 Jan;90(1):8–17. doi: 10.1530/acta.0.0900008. [DOI] [PubMed] [Google Scholar]
  9. Bertagna X., Luton J. P., Binoux M., Bricaire H., Girard F. Characterization of lipotropin-, corticotropin-, and beta-endorphin-immunoreactive materials secreted in vitro by a human pituitary adenoma responsible for a case of Nelson's syndrome. J Clin Endocrinol Metab. 1979 Oct;49(4):527–532. doi: 10.1210/jcem-49-4-527. [DOI] [PubMed] [Google Scholar]
  10. Besser G. M., Orth D. N., Nicholson W. E., Byyny R. L., Abe K., Woodham J. P. Dissociation of the disappearance of bioactive and radioimmunoreactive ACTH from plasma in man. J Clin Endocrinol Metab. 1971 May;32(5):595–603. doi: 10.1210/jcem-32-5-595. [DOI] [PubMed] [Google Scholar]
  11. Bloomfield G. A., Scott A. P., Lowry P. J., Gilkes J. J., Rees L. H. A reappraisal of human beta MSH. Nature. 1974 Dec 6;252(5483):492–493. doi: 10.1038/252492a0. [DOI] [PubMed] [Google Scholar]
  12. Chrétien M., Benjannet S., Dragon N., Seidah N. G., Lis M. Isolation of peptides with opiate activity from sheep and human pituitaries: relationship to beta-lipotropin. Biochem Biophys Res Commun. 1976 Sep 20;72(2):472–478. doi: 10.1016/s0006-291x(76)80066-6. [DOI] [PubMed] [Google Scholar]
  13. Chrétien M., Gilardeau C., Seidah N., Lis M. Purification and partial chemical characterization of human pituitary lipolytic hormone. Can J Biochem. 1976 Sep;54(9):778–782. doi: 10.1139/o76-111. [DOI] [PubMed] [Google Scholar]
  14. Crine P., Gianoulakis C., Seidah N. G., Gossard F., Pezalla P. D., Lis M., Chrétien M. Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4719–4723. doi: 10.1073/pnas.75.10.4719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cseh G., Barát E., Patthy A., Gráf L. Studies on the primary structure of human beta-lipotropic hormone. FEBS Lett. 1972 Apr 1;21(3):344–346. doi: 10.1016/0014-5793(72)80198-4. [DOI] [PubMed] [Google Scholar]
  16. Donald R. A., Toth A. A comparison of the -melanocyte-stimulating hormone and corticotropin response to hypoglycemia. J Clin Endocrinol Metab. 1973 May;36(5):925–930. doi: 10.1210/jcem-36-5-925. [DOI] [PubMed] [Google Scholar]
  17. Donnadieu M., Sevaux D. Radioimmunoassay of melanocytes-stimulating hormone (beta-MSH) in human plasma. Biomedicine. 1973 Jun 20;19(6):272–274. [PubMed] [Google Scholar]
  18. Gilardeau C., Chrétien M. Isolation and characterization of beta-lipolytic hormone from porcine pituitary gland. Can J Biochem. 1970 Sep;48(9):1017–1021. doi: 10.1139/o70-159. [DOI] [PubMed] [Google Scholar]
  19. Gilkes J. J., Bloomfield G. A., Scott A. P., Lowry P. J., Ratcliffe J. G., Landon J., Rees L. H. Development and validation of a radioimmunoassay for peptides related to beta-melanocyte-stimulating hormone in human plasma: the lipotropins. J Clin Endocrinol Metab. 1975 Mar;40(3):450–457. doi: 10.1210/jcem-40-3-450. [DOI] [PubMed] [Google Scholar]
  20. Gilkes J. J., Eady R. A., Rees L. H., Munro D. D., Moorhead J. F. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis. Br Med J. 1975 Mar 22;1(5959):656–657. doi: 10.1136/bmj.1.5959.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gilkes J. J., Rees L. H., Besser G. M. Plasma immunoreactive corticotrophin and lipotrophin in Cushing's syndrome and Addison's disease. Br Med J. 1977 Apr 16;1(6067):996–998. doi: 10.1136/bmj.1.6067.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hirata Y., Matsukura S., Imura H., Nakamura M., Tanaka A. Size heterogeneity of beta-MSH in ectopic ACTH-producing tumors: presence of beta-LPH-like peptide. J Clin Endocrinol Metab. 1976 Jan;42(1):33–40. doi: 10.1210/jcem-42-1-33. [DOI] [PubMed] [Google Scholar]
  23. Höllt V., Müller O. A., Fahlbusch R. beta-Endorphin in human plasma: basal and pathologically elevated levels. Life Sci. 1979 Jul 2;25(1):37–44. doi: 10.1016/0024-3205(79)90487-9. [DOI] [PubMed] [Google Scholar]
  24. Jeffcoate W. J., Rees L. H., Lowry P. J., Besser G. M. A specific radioimmunoassay for human beta-lipotropin. J Clin Endocrinol Metab. 1978 Jul;47(1):160–167. doi: 10.1210/jcem-47-1-160. [DOI] [PubMed] [Google Scholar]
  25. Krieger D. T., Liotta A. S., Suda T., Goodgold A., Condon E. Human plasma immunoreactive lipotropin and adrenocorticotropin in normal subjects and in patients with pituitary-adrenal disease. J Clin Endocrinol Metab. 1979 Apr;48(4):566–571. doi: 10.1210/jcem-48-4-566. [DOI] [PubMed] [Google Scholar]
  26. Krieger D. T., Liotta A., Li C. H. Human plasma immunoreactive beta-lipotropin: correlation with basal and stimulated plasma ACTH concentrations. Life Sci. 1977 Dec 15;21(12):1771–1777. doi: 10.1016/0024-3205(77)90157-6. [DOI] [PubMed] [Google Scholar]
  27. Li C. H., Barnafi L., Chrétien M., Chung D. Isolation and amino-acid sequence of beta-LPH from sheep pituitary glands. Nature. 1965 Dec 11;208(5015):1093–1094. doi: 10.1038/2081093b0. [DOI] [PubMed] [Google Scholar]
  28. Li C. H., Chung D., Doneen B. A. Isolation, characterization and opiate activity of beta-endorphin from human pituitary glands. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1542–1547. doi: 10.1016/s0006-291x(76)80189-1. [DOI] [PubMed] [Google Scholar]
  29. Li C. H., Chung D. Primary structure of human beta-lipotropin. Nature. 1976 Apr 15;260(5552):622–624. doi: 10.1038/260622a0. [DOI] [PubMed] [Google Scholar]
  30. Liotta A. S., Li C. H., Schussler G. C., Krieger D. T. Comparative metabolic clearance rate, volume of distribution and plasma half-life of human beta-lipotropin and ACTH. Life Sci. 1978 Dec 4;23(23):2323–2330. doi: 10.1016/0024-3205(78)90198-4. [DOI] [PubMed] [Google Scholar]
  31. Liotta A. S., Suda T., Krieger D. T. beta-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant beta-endorphin. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2950–2954. doi: 10.1073/pnas.75.6.2950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lohmar P., Li C. H. Isolation of bovine beta-lipotropic hormone. Biochim Biophys Acta. 1967 Oct 23;147(2):381–383. doi: 10.1016/0005-2795(67)90416-3. [DOI] [PubMed] [Google Scholar]
  33. Mains R. E., Eipper B. A. Coordinate synthesis of corticotropins and endorphins by mouse pituitary tumor cells. J Biol Chem. 1978 Feb 10;253(3):651–655. [PubMed] [Google Scholar]
  34. Nakao K., Nakai Y., Jingami H., Oki S., Fukata J., Imura H. Substantial rise of plasma beta-endorphin levels after insulin-induced hypoglycemia in human subjects. J Clin Endocrinol Metab. 1979 Dec;49(6):838–841. doi: 10.1210/jcem-49-6-838. [DOI] [PubMed] [Google Scholar]
  35. Nakao K., Nakai Y., Oki S., Horii K., Imura H. Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration. J Clin Invest. 1978 Dec;62(6):1395–1398. doi: 10.1172/JCI109261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Reichlin M., Schnure J. J., Vance V. K. Induction of antibodies to porcine ACTH in rabbits with nonsteroidogenic polymers of BSA and ACTH. Proc Soc Exp Biol Med. 1968 Jun;128(2):347–350. doi: 10.3181/00379727-128-33011. [DOI] [PubMed] [Google Scholar]
  37. Reiss E., Canterbury J. M. Emerging concepts of the nature of circulating parathyroid hormones: implications for clinical research. Recent Prog Horm Res. 1974;30(0):391–429. doi: 10.1016/b978-0-12-571130-2.50014-6. [DOI] [PubMed] [Google Scholar]
  38. Rubenstein A. H., Steiner D. F., Horwitz D. L., Mako M. E., Block M. B., Starr J. I., Kuzuya H., Melani F. Clinical significance of circulating proinsulin and C-peptide. Recent Prog Horm Res. 1976;33:435–475. doi: 10.1016/b978-0-12-571133-3.50017-9. [DOI] [PubMed] [Google Scholar]
  39. Rubinstein M., Stein S., Gerber L. D., Udenfriend S. Isolation and characterization of the opioid peptides from rat pituitary: beta-lipotropin. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3052–3055. doi: 10.1073/pnas.74.7.3052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Scott A. P., Lowry P. J. Adrenocorticotrophic and melanocyte-stimulating peptides in the human pituitary. Biochem J. 1974 Jun;139(3):593–602. doi: 10.1042/bj1390593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Smith A. G., Shuster S., Comaish J. S., Plummer N. A., Thody A. J., Alvarez-Ude F., Kerr D. N. Plasma immunoreactive beta-melanocyte-stimulating hormone and skin pigmentation in chronic renal failure. Br Med J. 1975 Mar 22;1(5959):658–659. doi: 10.1136/bmj.1.5959.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Suda T., Liotta A. S., Krieger D. T. beta-Endorphin is not detectable in plasma from normal human subjects. Science. 1978 Oct 13;202(4364):221–223. doi: 10.1126/science.211585. [DOI] [PubMed] [Google Scholar]
  43. Tanaka K., Nicholson W. E., Orth D. N. Diurnal rhythm and disappearance half-time of endogenous plasma immunoreactive beta-MSH (LPH) and ACTH in man. J Clin Endocrinol Metab. 1978 Jun;46(6):883–890. doi: 10.1210/jcem-46-6-883. [DOI] [PubMed] [Google Scholar]
  44. Tanaka K., Nicholson W. E., Orth D. N. The nature of the immunoreactive lipotropins in human plasma and tissue extracts. J Clin Invest. 1978 Jul;62(1):94–104. doi: 10.1172/JCI109119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tanaka K., Orth D. N. The detection of "purified" incubation damage by several radioimmunoassay separation methods. J Lab Clin Med. 1978 Jun;91(6):881–892. [PubMed] [Google Scholar]
  46. Thody A. J., Plummer N. A. A radioimmunoassay for beta-melanocyte-stimulating hormone in human plasma. J Endocrinol. 1973 Aug;58(2):263–273. [PubMed] [Google Scholar]
  47. Wardlaw S. L., Frantz A. G. Measurement of beta-endorphin in human plasma. J Clin Endocrinol Metab. 1979 Jan;48(1):176–180. doi: 10.1210/jcem-48-1-176. [DOI] [PubMed] [Google Scholar]
  48. Wiedemann E., Saito T., Linfoot J. A., Li C. H. Radioimmunoassay of human beta-lipotropin in unextracted plasma. J Clin Endocrinol Metab. 1977 Nov;45(5):1108–1111. doi: 10.1210/jcem-45-5-1108. [DOI] [PubMed] [Google Scholar]
  49. Wiedemann E., Saito T., Linfoot J. A., Li C. H. Specific radioimmunoassay of human beta-endorphin in unextracted plasma. J Clin Endocrinol Metab. 1979 Sep;49(3):478–480. doi: 10.1210/jcem-49-3-478. [DOI] [PubMed] [Google Scholar]
  50. Yoshimi H., Matsukura S., Sueoka S., Fukase M., Yokota M., Hirata Y., Imura H. Radioimmunoassay for beta-endorphin: presence of immunoreactive "big-big" beta-endorphin ("big" beta-lipotropin) in human and rat pituitaries. Life Sci. 1978 Jun 26;22(24):2189–2195. doi: 10.1016/0024-3205(78)90570-2. [DOI] [PubMed] [Google Scholar]

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