Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors.
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.
Szabó
Peter M
PM
2nd Department of Medicine, Faculty of Medicine, Semmelweis University, 1088 Budapest, Szentkirályi str. 46, Hungary.
Wiener
Zoltán
Z
Tömböl
Zsófia
Z
Kovács
Attila
A
Pócza
Péter
P
Horányi
János
J
Kulka
Janina
J
Riesz
Peter
P
Tóth
Miklós
M
Patócs
Attila
A
Gaillard
Rolf C
RC
Falus
András
A
Rácz
Károly
K
Igaz
Peter
P
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000235:genetics / Q000378:metabolism; D000074040:Receptors, Histamine H4
C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D006632:Histamine; D006640:Histidine Decarboxylase