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

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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.

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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

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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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Authors and Affiliations

  1. 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 1088, Budapest, Szentkirályi str. 46, Hungary

    Peter M. Szabó, Zsófia Tömböl, Miklós Tóth, Károly Rácz & Peter Igaz

  2. Department of Genetics, Cell and Immunobiology Faculty of Medicine, Semmelweis University, 1089, Budapest, Nagyvárad square 4, Hungary

    Zoltán Wiener, Péter Pócza & András Falus

  3. 2nd Department of Pathology Faculty of Medicine, Semmelweis University, 1091, Budapest, Üllői str. 93, Hungary

    Attila Kovács & Janina Kulka

  4. 1st Department of Surgery, Faculty of Medicine, Semmelweis University, Üllői str. 78, 1083, Budapest, Hungary

    János Horányi

  5. Department of Urology, Faculty of Medicine, Semmelweis University, 1082, Budapest, Üllői str. 78/B, Hungary

    Peter Riesz

  6. Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, 1088, Budapest, Szentkirályi str. 46, Hungary

    Attila Patócs

  7. Service d’Endocrinologie, Diabétologie et Métabolisme, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne, Rue de Bugnon 46, Switzerland

    Rolf C. Gaillard

  8. Inflammation Biology and Immune Genomics Research Group, Hungarian Academy of Sciences and Semmelweis University, 1089, Budapest, Nagyvárad square 4, Hungary

    András Falus

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  1. Peter M. Szabó
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  2. Zoltán Wiener
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Correspondence to Peter Igaz.

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Szabó, P.M., Wiener, Z., Tömböl, Z. et al. Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors. Virchows Arch 455, 133–142 (2009). https://doi.org/10.1007/s00428-009-0807-x

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  • DOI: https://doi.org/10.1007/s00428-009-0807-x

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