Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(3):1057–1060. doi: 10.1073/pnas.87.3.1057

Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide.

E M Smith 1, F S Galin 1, R D LeBoeuf 1, D H Coppenhaver 1, D V Harbour 1, J E Blalock 1
PMCID: PMC53409  PMID: 1689057

Abstract

To determine the degree of similarity between pituitary and lymphocyte proopiomelanocortin, the lymphocyte mRNA was reverse transcribed, cloned, and sequenced. Murine lymphocyte mRNA was first purified by oligo(dT)-cellulose affinity chromatography and was reverse transcribed by using a selective 3' antisense oligonucleotide primer directed at the boundary between the translated/nontranslated region on the 3' end of exon 3. This cDNA was then amplified in a polymerase chain reaction with selective primers containing Sal I and Kpn I restriction endonuclease sites. Amplified cDNA was then directionally ligated into M13mp18 and M13mp19 bacteriophage and was sequenced. The nucleotide sequence encoding this peptide was identical to that of mouse pituitary corticotropin (ACTH). Elevated levels of lymphocyte immunoreactive ACTH were then induced with bacterial lipopolysaccharide and the peptide(s) was purified by antibody affinity chromatography and reverse-phase high-performance liquid chromatography. The predominant immunoreactive ACTH species was approximately 3 kDa and its sequence was identical to pituitary ACTH(1-25). These results conclusively demonstrate that lymphocytes produce authentic ACTH and harbor its mRNA.

Full text

PDF
1059

Images in this article

1058Image
on p.1058
1058Image
on p.1058

Selected References

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

  1. Alvarez-Mon M., Kehrl J. H., Fauci A. S. A potential role for adrenocorticotropin in regulating human B lymphocyte functions. J Immunol. 1985 Dec;135(6):3823–3826. [PubMed] [Google Scholar]
  2. Blalock J. E. A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiol Rev. 1989 Jan;69(1):1–32. doi: 10.1152/physrev.1989.69.1.1. [DOI] [PubMed] [Google Scholar]
  3. Blalock J. E., Smith E. M. A complete regulatory loop between the immune and neuroendocrine systems. Fed Proc. 1985 Jan;44(1 Pt 1):108–111. [PubMed] [Google Scholar]
  4. Buzzetti R., McLoughlin L., Lavender P. M., Clark A. J., Rees L. H. Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. J Clin Invest. 1989 Feb;83(2):733–737. doi: 10.1172/JCI113940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DuPont A. G., Somers G., Van Steirteghem A. C., Warson F., Vanhaelst L. Ectopic adrenocorticotropin production: disappearance after removal of inflammatory tissue. J Clin Endocrinol Metab. 1984 Apr;58(4):654–658. doi: 10.1210/jcem-58-4-654. [DOI] [PubMed] [Google Scholar]
  6. Farrar W. L., Hill J. M., Harel-Bellan A., Vinocour M. The immune logical brain. Immunol Rev. 1987 Dec;100:361–378. doi: 10.1111/j.1600-065x.1987.tb00539.x. [DOI] [PubMed] [Google Scholar]
  7. Fehm H. L., Holl R., Späth-Schwalbe E., Born J., Voigt K. H. Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin. Life Sci. 1988;42(6):679–686. doi: 10.1016/0024-3205(88)90459-6. [DOI] [PubMed] [Google Scholar]
  8. Harbour-McMenamin D., Smith E. M., Blalock J. E. Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins. Infect Immun. 1985 Jun;48(3):813–817. doi: 10.1128/iai.48.3.813-817.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harbour D. V., Smith E. M., Blalock J. E. Novel processing pathway for proopiomelanocortin in lymphocytes: endotoxin induction of a new prohormone-cleaving enzyme. J Neurosci Res. 1987;18(1):95–101. doi: 10.1002/jnr.490180116. [DOI] [PubMed] [Google Scholar]
  10. Johnson E. W., Blalock J. E., Smith E. M. ACTH receptor-mediated induction of leukocyte cyclic AMP. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1205–1211. doi: 10.1016/s0006-291x(88)81002-7. [DOI] [PubMed] [Google Scholar]
  11. Johnson H. M., Smith E. M., Torres B. A., Blalock J. E. Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4171–4174. doi: 10.1073/pnas.79.13.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson H. M., Torres B. A., Smith E. M., Dion L. D., Blalock J. E. Regulation of lymphokine (gamma-interferon) production by corticotropin. J Immunol. 1984 Jan;132(1):246–250. [PubMed] [Google Scholar]
  13. Li C. H. Adrenocorticotropin 45. Revised amino acid sequences for sheep and bovine hormones. Biochem Biophys Res Commun. 1972 Nov 1;49(3):835–839. doi: 10.1016/0006-291x(72)90486-x. [DOI] [PubMed] [Google Scholar]
  14. Lolait S. J., Clements J. A., Markwick A. J., Cheng C., McNally M., Smith A. I., Funder J. W. Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. J Clin Invest. 1986 Jun;77(6):1776–1779. doi: 10.1172/JCI112501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lolait S. J., Lim A. T., Toh B. H., Funder J. W. Immunoreactive beta-endorphin in a subpopulation of mouse spleen macrophages. J Clin Invest. 1984 Jan;73(1):277–280. doi: 10.1172/JCI111203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meyer W. J., 3rd, Smith E. M., Richards G. E., Cavallo A., Morrill A. C., Blalock J. E. In vivo immunoreactive adrenocorticotropin (ACTH) production by human mononuclear leukocytes from normal and ACTH-deficient individuals. J Clin Endocrinol Metab. 1987 Jan;64(1):98–105. doi: 10.1210/jcem-64-1-98. [DOI] [PubMed] [Google Scholar]
  17. Nagle G. T., Painter S. D., Blankenship J. E., Dixon J. D., Kurosky A. Evidence for the expression of three genes encoding homologous atrial gland peptides that cause egg laying in Aplysia. J Biol Chem. 1986 Jun 15;261(17):7853–7859. [PubMed] [Google Scholar]
  18. Notake M., Tobimatsu T., Watanabe Y., Takahashi H., Mishina M., Numa S. Isolation and characterization of the mouse corticotropin-beta-lipotropin precursor gene and a related pseudogene. FEBS Lett. 1983 May 30;156(1):67–71. doi: 10.1016/0014-5793(83)80250-6. [DOI] [PubMed] [Google Scholar]
  19. Oates E. L., Allaway G. P., Armstrong G. R., Boyajian R. A., Kehrl J. H., Prabhakar B. S. Human lymphocytes produce pro-opiomelanocortin gene-related transcripts. Effects of lymphotropic viruses. J Biol Chem. 1988 Jul 25;263(21):10041–10044. [PubMed] [Google Scholar]
  20. Riniker B., Sieber P., Rittel W., Zuber H. Revised amino-acid sequences for porcine and human adrenocorticotrophic hormone. Nat New Biol. 1972 Jan 26;235(56):114–115. doi: 10.1038/newbio235114b0. [DOI] [PubMed] [Google Scholar]
  21. Smith E. M., Blalock J. E. A molecular basis for interactions between the immune and neuroendocrine systems. Int J Neurosci. 1988 Feb;38(3-4):455–464. doi: 10.3109/00207458808990706. [DOI] [PubMed] [Google Scholar]
  22. Smith E. M., Blalock J. E. Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7530–7534. doi: 10.1073/pnas.78.12.7530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith E. M., Brosnan P., Meyer W. J., Blalock J. E. An ACTH receptor on human mononuclear leukocytes. Relation to adrenal ACTH-receptor activity. N Engl J Med. 1987 Nov 12;317(20):1266–1269. doi: 10.1056/NEJM198711123172006. [DOI] [PubMed] [Google Scholar]
  24. Smith E. M., Meyer W. J., Blalock J. E. Virus-induced corticosterone in hypophysectomized mice: a possible lymphoid adrenal axis. Science. 1982 Dec 24;218(4579):1311–1312. doi: 10.1126/science.6183748. [DOI] [PubMed] [Google Scholar]
  25. Smith E. M., Morrill A. C., Meyer W. J., 3rd, Blalock J. E. Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins. 1986 Jun 26-Jul 2Nature. 321(6073):881–882. doi: 10.1038/321881a0. [DOI] [PubMed] [Google Scholar]
  26. Uhler M., Herbert E. Complete amino acid sequence of mouse pro-opiomelanocortin derived from the nucleotide sequence of pro-opiomelanocortin cDNA. J Biol Chem. 1983 Jan 10;258(1):257–261. [PubMed] [Google Scholar]
  27. Westly H. J., Kleiss A. J., Kelley K. W., Wong P. K., Yuen P. H. Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. J Exp Med. 1986 Jun 1;163(6):1589–1594. doi: 10.1084/jem.163.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES