Skip to main content
SpringerLink
Log in

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Cite this article

Abstract

Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC–ESI-MS–MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making.

Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Scheme 2
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Santagata S, Eberlin LS, Norton I, Calligaris D, Feldman DR, Ide JL, Liu X, Wiley JS, Vestal ML, Ramkissoon SH, Orringer DA, Gilla KK, Dunn IF, Dias-Santagata D, Ligon KL, Jolesz FA, Golby AJ, Cooks RG, Agar NYR (2014) Proc Natl Acad Sci U S A 111:11121–11126

    Article  CAS  Google Scholar 

  2. Balog J, Sasi-Szabo L, Kinross J, Lewis MR, Muirhead LJ, Veselkov K, Mirnezami R, Dezso B, Damjanovich L, Darzi A, Nicholson JK, Takats Z (2013) Sci Trans Med 5:194ra93

    Article  Google Scholar 

  3. Goodman S, O’Connor A, Kandil D, Khan A (2014) Arch Pathol Lab Med 138:57–64

    Article  Google Scholar 

  4. Rey-Dios R, Hattab EM, Cohen-Gadol AA (2014) Acta Neurochir 156:1071–1075

    Article  Google Scholar 

  5. Spicer J, Benay C, Lee L, Rousseau M, Andalib A, Kushner Y, Marcus V, Ferri L (2014) Ann Surg Oncol 21:2580–2586

    Article  Google Scholar 

  6. Ramos-Vara JA, Miller MA (2014) Vet Pathol 51:42–87

    Article  CAS  Google Scholar 

  7. Eberlin LS, Norton I, Dill AL, Golby AJ, Ligon KL, Santagata S, Cooks RG, Agar NYR (2012) Cancer Res 72:645–654

    Article  CAS  Google Scholar 

  8. Eberlin LS, Liu XH, Ferreira CR, Santagata S, Agar NYR, Cooks RG (2011) Anal Chem 83:8366–8371

    Article  CAS  Google Scholar 

  9. Calligaris D, Caragacianu D, Liu X, Norton I, Thompson CJ, Richardson AL, Golshan M, Easterling ML, Santagata S, Dillon DA, Jolesz FA, Agara NYR (2014) Proc Natl Acad Sci U S A 111:15184–15189

    Article  CAS  Google Scholar 

  10. Balog J, Szaniszlo T, Schaefer KC, Denes J, Lopata A, Godorhazy L, Szalay D, Balogh L, Sasi-Szabo L, Toth M, Takats Z (2010) Anal Chem 82:7343–7350

    Article  CAS  Google Scholar 

  11. Kertesz V, Van Berkel GJ, Vavrek M, Koeplinger KA, Schneider BB, Covey TR (2008) Anal Chem 80:5168–5177

    Article  CAS  Google Scholar 

  12. Van Berkel GJ, Pasilis SP, Ovchinnikova O (2008) J Mass Spectrom 43:1161–1180

    Article  Google Scholar 

  13. Van Berkel GJ, Sanchez AD, Quirke JME (2002) Anal Chem 74:6216–6223

    Article  Google Scholar 

  14. Van Berkel GJ, Kertesz V, King RC (2009) Anal Chem 81:7096–7101

    Article  Google Scholar 

  15. Van Berkel GJ, Kertesz V, Koeplinger KA, Vavrek M, Kong AT (2008) J Mass Spectrom 43:500–508

    Article  Google Scholar 

  16. Kertesz V, Van Berkel GJ (2010) J Mass Spectrom 45:252–260

    Article  CAS  Google Scholar 

  17. Edwards RL, Griffiths P, Bunch J, Cooper HJ (2014) Proteomics 14:1232–1238

    Article  CAS  Google Scholar 

  18. Randall EC, Bunch J, Cooper HJ (2014) Anal Chem 86:10504–10510

    Article  CAS  Google Scholar 

  19. Sarsby J, Martin NJ, Lalor PF, Bunch J, Cooper HJ (2014) J Am Soc Mass Spectrom 25:1953–1961

    Article  CAS  Google Scholar 

  20. Martin NJ, Bunch J, Cooper HJ (2013) J Am Soc Mass Spectrom 24:1242–1249

    Article  CAS  Google Scholar 

  21. Edwards RL, Creese AJ, Baumert M, Griffiths P, Bunch J, Cooper HJ (2011) Anal Chem 83:2265–2270

    Article  CAS  Google Scholar 

  22. Edwards RL, Griffiths P, Bunch J, Cooper HJ (2012) J Am Soc Mass Spectrom 23:1921–1930

    Article  CAS  Google Scholar 

  23. Rao W, Celiz AD, Scurr DJ, Alexander MR, Barrett DA (2013) J Am Soc Mass Spectrom 24:1927–1936

    Article  CAS  Google Scholar 

  24. Tomlinson L, Fuchser J, Futterer A, Baumert M, Hassall DG, West A, Marshall PS (2014) Rapid Commun Mass Spectrom 28:995–1003

    Article  CAS  Google Scholar 

  25. Geho MD, Espina V, Liotta LA, Petricoin EF, Wulfkuhle JD (2008) Chapter 9. “Clinical Proteomics”. In: Cheng L, Zhang DY (eds) Molecular Genetic Pathology. Humana Press, Totowa

    Google Scholar 

  26. Masucci JA, Mahan AD, Kwasnoski JD, Caldwell GW (2012) Curr Top Med Chem 12:1243–1249

    Article  CAS  Google Scholar 

  27. Ackermann BL, Berna MJ, Eckstein JA, Ott LW, Chaudhary AK (2008) Ann Rev Anal Chem 1:357–396

    Article  CAS  Google Scholar 

  28. Kertesz V, Van Berkel GJ (2010) Anal Chem 82:5917–5921

    Article  CAS  Google Scholar 

  29. Kertesz V, Van Berkel GJ (2013) Bioanalysis 5:819–826

    Article  CAS  Google Scholar 

  30. Van Berkel GJ, Kertesz V (2013) Rapid Commun Mass Spectrom 27:1329–1334

    Article  Google Scholar 

  31. Kertesz V, Paranthaman N, Moench P, Catoire A, Flarakos J, Van Berkel GJ (2014) Bioanalysis 6:2599–2606

    Article  CAS  Google Scholar 

  32. Kertesz V, Weiskittel TM, Van Berkel GJ (2015) Anal Bioanal Chem 407:2117–2125

    Article  CAS  Google Scholar 

  33. Abu-Rabie P, Spooner N (2011) Bioanalysis 3:2769–2781

    Article  CAS  Google Scholar 

  34. Heinig K, Wirz T, Gajate-Perez A (2010) Bioanalysis 2:1873–1882

    Article  CAS  Google Scholar 

  35. Kertesz V, Van Berkel GJ (2014) Rapid Commun Mass Spectrom 28:1553–1560

    Article  CAS  Google Scholar 

  36. Calligaris D, Norton I, Feldman DR, Ide JL, Dunn IF, Eberlin LS, Cooks RG, Jolesz FA, Golby AJ, Santagata S, Agar NY (2013) J Mass Spectrom 48:1178–1187

    Article  CAS  Google Scholar 

  37. http://www.openscad.org. Last checked on May 1, 2015. OpenSCAD is Free Software released under the General Public License version 2

  38. Aihara H, Tamaki N, Ueyama T, Ishihara Y, Kondoh T (1996) Neuro Surg 24:1119–1123

    CAS  Google Scholar 

  39. Flitsch J, Schmid SM, Bernreuther C, Winterberg B, Ritter MM, Lehnert H, Burkhardt T (2014) Pituitary 18:279–282

    Article  Google Scholar 

  40. http://www.waters.com/webassets/cms/library/docs/720002064en.pdf. Last checked on May 1, 2015

  41. Nussey S, Whitehead S (2001) Endocrinology: An Integrated Approach, Chapter 7: The pituitary gland. BIOS Scientific Publishers, Oxford

    Book  Google Scholar 

Download references

Acknowledgments

This project was supported by AB Sciex through a Cooperative Research and Development Agreement (CRADA NFE-10-02966). The API 4000 used in this work was provided on loan from AB Sciex as part of the CRADA. NYRA was supported by the Daniel E. Ponton Fund for the Neurosciences, the DFCI Pediatric Low-Grade Astrocytoma (PLGA) Program, and the NIH Director’s New Innovator Award (Grant 1DP2OD007383‐01). The authors would like to thank Aaron Bickel, James Glick, and Jimmy Flarakos from Novartis Institutes for Biomedical Research (Cambridge, MA) for their valuable help in 3D printing of the custom tray. ORNL is managed by UT-Battelle, LLC for the U.S. Department of Energy under contract DE-AC05-00OR22725.

Author information

Authors and Affiliations

  1. Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37831-6131, USA

    Vilmos Kertesz & Gary J. Van Berkel

  2. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115-6110, USA

    David Calligaris, Daniel R. Feldman, Armen Changelian, Edward R. Laws & Nathalie Y. R. Agar

  3. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115-6110, USA

    Sandro Santagata

  4. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115-6110, USA

    Nathalie Y. R. Agar

Authors
  1. Vilmos Kertesz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Calligaris
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel R. Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Armen Changelian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Edward R. Laws
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sandro Santagata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nathalie Y. R. Agar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary J. Van Berkel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Vilmos Kertesz or Nathalie Y. R. Agar.

Additional information

This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1.25 MB)

(MPG 30.8 MB)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kertesz, V., Calligaris, D., Feldman, D.R. et al. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS. Anal Bioanal Chem 407, 5989–5998 (2015). https://doi.org/10.1007/s00216-015-8803-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-8803-2

Keywords

search

Navigation