Endocrine Abstracts (2008) 16 P292

Different gene expression patterns of histamine related genes in human adrenocortical tumors

Peter Szabó1, Zoltán Wiener2, Zsófia Tömböl1, Gergely Tölgyesi2, János Horányi3, Rolf C Gaillard4, András Falus2, Károly Rácz1 & Peter Igaz1


12nd Department of Medicine, Semmelweis University, Budapest, Hungary; 2Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; 31st Department of Surgery, Semmelweis University, Budapest, Hungary; 4Department of Endocrinology, Diabetology and Metabolism, University Hospital, Lausanne, Switzerland.


Introduction: The pathogenesis of sporadic adrenocortical tumors is poorly elucidated. Considering the importance of the adrenal cortex at the immune-neuroendocrine interface and the known actions of immune mediators on adrenocortical cell functioning, we supposed that immune or inflammatory factors might be involved in the pathogenesis of these tumors. Gene expression patterns of various inflammatory and immune mediators were studied by a functional genomics/bioinformatics approach.

Methods: Hormonally inactive, cortisol-, aldosterone-secreting benign and malignant adrenocortical tumors, and normal adrenocortical tissues were studied. Both 8×1.5 K custom microarrays focusing on immune-related genes and whole genome 4×44 K microarrays were performed in 6–10 samples of each group. Real-time RT-PCR and western-blotting were used for the validation of results.

Results: Seventy genes showed significant (P<0.05, min. 2–2.5 fold) differences. Among these, histidine decarboxylase (HDC) and histamine receptors were noteworthy, as no previous data described the involvement of histamine in adrenocortical tumorigenesis. Therefore, we examined and validated the expression of all genes involved in histamine biosynthesis, action and degradation. HDC expression was highest in normal tissues, whereas hardly detectable in tumor samples. Histamine H2 receptor expression was the highest in normal tissues too, its expression was lower in hormonally inactive, and much lower in hormone-secreting and malignant tumors. Histamine H4 receptor could not be detected in cortisol-secreting tumors, however, it was moderately expressed in other samples.

Discussion: Our findings raise the possibility that adrenocortical tumorigenesis might be characterized by reduced histamine biosynthesis and action.

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