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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

Abstract

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.

Keywords

Adrenal cortex Adrenocortical tumor Histamine mRNA Protein Receptor 

Abbreviations

ACC

Adrenocortical carcinoma

ACTH

Adrenocorticotropin

APA

Aldosterone producing adenoma

cAMP

Cyclic AMP

CPA

Cortisol-producing adenoma

DAO

Diamino-oxydase

DHEA

Dehydroepiandrosterone

DHEAS

Dehydroepiandrosterone sulfate

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

HDC

Histidine decarboxylase

HNMT

Histamine-N-methyltransferase

HRH1

Histamine receptor H1

HRH2

Histamine receptor H2

HRH3

Histamine receptor H3

HRH4

Histamine receptor H4

IA

Hormonally inactive adenoma

IFN-γ

Interferon-γ

IL-10

Interleukin-10

IL-12

Interleukin-12

PKA

cAMP-dependent protein kinase

PRKAR1A

Protein kinase A regulatory-subunit type-I alpha

QRT-PCR

Quantitative real-time RT-PCR

Notes

Acknowledgements

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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