Gene expression profiles in aldosterone-producing adenomas and adjacent adrenal glands.
BACKGROUND
Primary aldosteronism (PA) is the most common form of endocrine hypertension affecting ∼8-10% of hypertensive subjects. Aldosterone production in PA occurs under low-renin conditions, and the mechanisms that maintain the production of aldosterone in PA remain unknown. Objective This study was designed to compare the transcript profiles between aldosterone-producing adenoma (APA) and their adjacent adrenal gland (AAG) from the same adrenal.


METHODS
Total RNA was extracted from ten APA and ten AAG; and subsequently analyzed by microarray and real-time quantitative RT-PCR (qPCR). The microarray data were paired for each APA-AAG, and analyzed by GeneSpring GX 11 with paired t-test and fold change calculations for each transcript. Changes identified by microarray analysis were confirmed by qPCR.


RESULTS
Microarray analysis indicated that 14 genes had significantly up-regulated expression in APA compared to AAG. Among the elevated genes were aldosterone synthase (CYP11B2) as well as novel transcription factors, calmodulin-binding proteins, and other genes that have not been previously studied in APA. Selective analysis of 11 steroidogenic enzymes using microarray demonstrated that only CYP11B2 showed a significantly higher transcript level in APA compared to AAG (P<0.001). In contrast, AKR1C3 (17β-hydroxysteroid dehydrogenase type 5), CYP17 (17α-hydroxylase/17,20 lyase), and CYB5 (cytochrome b5) showed significantly lower transcript level in APA (P<0.05).


CONCLUSIONS
The transcriptome analysis of APA compared with AAG showed several novel genes that are associated with APA phenotype. This gene list provides new candidates for the elucidation of the molecular mechanisms leading to PA.
Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
Tao
T
Wang
Fumitoshi
F
Satoh
Ryo
R
Morimoto
Yasuhiro
Y
Nakamura
Hironobu
H
Sasano
Richard J
RJ
Auchus
Michael A
MA
Edwards
William E
WE
Rainey
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000236:Adenoma / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000074425:Aldo-Keto Reductase Family 1 Member C3; D000450:Aldosterone / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D000450:Aldosterone; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2
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