Expression profiles for steroidogenic enzymes in adrenocortical disease.
BACKGROUND
Excess production of aldosterone or cortisol has profound effects on cardiovascular function and impacts other major organ systems. The mechanisms leading to the autonomous hypersecretion of aldosterone or cortisol in aldosterone-producing adenoma (APA) or cortisol-producing adenoma (CPA) are unknown.


OBJECTIVE
The objective of this study was to compare the expression profiles of several steroid-metabolizing enzymes and transcription factors from normal adrenal (NA), APAs, and CPAs.


METHODS
RNA from NAs, APAs, and CPAs were analyzed by microarray and real-time RT-PCR.


METHODS
This study was performed at academic research laboratories.


METHODS
At least nine normal controls and 12 patients with APA or CPA were studied.


METHODS
There was no intervention procedure.


METHODS
The main outcome measure was the expression of steroidogenic enzymes in adrenocortical disease.


RESULTS
A microarray indicated a greater than 3-fold increase in the expression of CYP11B2 (aldosterone synthase) in APA, whereas 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) and HSD17B1 had greater than 3-fold increases in expression in CPA compared with NA. Real-time RT-PCR showed that APAs produced higher levels of HSD3B2, CYP21 (21-hydroxylase), and CYP11B2 mRNA, whereas CPAs produced higher levels of CYP11A (cholesterol side-chain cleavage), CYP17 (17alpha-hydroxylase/17-20 lyase), HSD3B2, and CYP11B1 (11beta-hydroxylase) mRNA compared with normal adrenal. Steroidogenic factor-1, DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome gene 1), and GATA-6 were expressed at higher levels in APAs and CPAs, whereas NURR1 was expressed at higher levels in APAs than in CPAs or NAs.


CONCLUSIONS
Elevated production of aldosterone in APAs and of cortisol in CPAs is associated with increased expression of enzymes needed for corticosteroid production along with alterations in transcription factors that enhance the expression of steroid-metabolizing enzymes.
Divisions of Reproductive and Pediatric Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
Mary H
MH
Bassett
Bobbie
B
Mayhew
Khurram
K
Rehman
Perrin C
PC
White
Franco
F
Mantero
Giorgio
G
Arnaldi
Paul M
PM
Stewart
Iwona
I
Bujalska
William E
WE
Rainey
D000236:Adenoma / Q000201:enzymology* / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000306:Adrenal Cortex Neoplasms / Q000201:enzymology* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D016022:Case-Control Studies; D003199:Computer Systems; D004798:Enzymes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D004798:Enzymes; C515057:NR5A1 protein, human; D012333:RNA, Messenger; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000450:Aldosterone; D006854:Hydrocortisone