Virchows Archiv

, Volume 455, Issue 2, pp 133–142 | Cite as

Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors

  • Peter M. Szabó
  • Zoltán Wiener
  • Zsófia Tömböl
  • Attila Kovács
  • Péter Pócza
  • János Horányi
  • Janina Kulka
  • Peter Riesz
  • Miklós Tóth
  • Attila Patócs
  • Rolf C. Gaillard
  • András Falus
  • Károly Rácz
  • Peter IgazEmail author
Original Article


Histamine is involved in the pathogenesis of several tumors; however, there are no data on its possible involvement in human adrenocortical tumorigenesis. The expression of genes and proteins involved in the biosynthesis (histidine decarboxylase, HDC), action (histamine receptors: HRH1–HRH4), and metabolism of histamine is largely unknown both in the normal human adrenal cortex and in adrenocortical tumors. In this study, we examined the expression of histamine-related genes and proteins and histamine content in normal adrenal cortex, benign adrenocortical adenomas, and malignant adrenocortical cancer (ACC). Fifteen normal adrenals and 43 tumors were studied. mRNA expression was examined by real time RT-PCR. Western-blotting and immunohistochemistry were used for the study of proteins. Tissue histamine content was determined by enzyme-linked immunosorbent assay. We found that all proteins involved in histamine biosynthesis and action are present both in the normal adrenal cortex and in the tumors studied. HDC expression and histamine content was highest in the normal tissues and lower in benign tumors, whereas it was significantly less in ACCs. HRH3 expression was significantly higher in ACC samples than in the other groups. Adrenocortical tumorigenesis might, thus, be characterized by reduced histamine biosynthesis; furthermore, different adrenocortical tumor subtypes may show unique histamine receptor expression profiles.


Adrenal cortex Adrenocortical tumor Histamine mRNA Protein Receptor 



Adrenocortical carcinoma




Aldosterone producing adenoma


Cyclic AMP


Cortisol-producing adenoma






Dehydroepiandrosterone sulfate


Glyceraldehyde-3-phosphate dehydrogenase


Histidine decarboxylase




Histamine receptor H1


Histamine receptor H2


Histamine receptor H3


Histamine receptor H4


Hormonally inactive adenoma








cAMP-dependent protein kinase


Protein kinase A regulatory-subunit type-I alpha


Quantitative real-time RT-PCR



Hungarian Ministry of Health 089/2006, Semmelweis University Research Grant, Hungarian Scientific Research Fund (OTKA) PD72306, Swiss National Fund (FNRS) 3200BO-105657/1) and Fondation pour la Recherche en Endocrinologie, Diabétologie et Métabolisme. Attila Patócs MD PhD is a recipient of a János Bolyai Research Grant. The authors would also like to thank Dr. Gábor L. Kovács (National Health Center, Budapest, Hungary) for supplying some tissue samples.

Conflict of interest

The authors have no conflict of interest to report.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Peter M. Szabó
    • 1
  • Zoltán Wiener
    • 2
  • Zsófia Tömböl
    • 1
  • Attila Kovács
    • 3
  • Péter Pócza
    • 2
  • János Horányi
    • 4
  • Janina Kulka
    • 3
  • Peter Riesz
    • 5
  • Miklós Tóth
    • 1
  • Attila Patócs
    • 6
  • Rolf C. Gaillard
    • 7
  • András Falus
    • 2
    • 8
  • Károly Rácz
    • 1
  • Peter Igaz
    • 1
    Email author
  1. 1.2nd Department of Medicine, Faculty of MedicineSemmelweis UniversityBudapestHungary
  2. 2.Department of Genetics, Cell and Immunobiology Faculty of MedicineSemmelweis UniversityBudapestHungary
  3. 3.2nd Department of Pathology Faculty of MedicineSemmelweis UniversityBudapestHungary
  4. 4.1st Department of Surgery, Faculty of MedicineSemmelweis UniversityBudapestHungary
  5. 5.Department of Urology, Faculty of MedicineSemmelweis UniversityBudapestHungary
  6. 6.Molecular Medicine Research GroupHungarian Academy of Sciences and Semmelweis UniversityBudapestHungary
  7. 7.Service d’Endocrinologie, Diabétologie et MétabolismeCentre Hospitalier Universitaire VaudoisLausanneSwitzerland
  8. 8.Inflammation Biology and Immune Genomics Research GroupHungarian Academy of Sciences and Semmelweis UniversityBudapestHungary

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