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Submitted on April 18, 2005
Accepted on June 21, 2005
Divisions of Reproductive and Pediatric Endocrinology, UT Southwestern Medical Center, Dallas, TX; Division of Endocrinology, Univ of Padua, Padua, Italy and Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
* To whom correspondence should be addressed. E-mail: william.rainey{at}utsouthwestern.edu.
Context: 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: To compare the expression profiles of several steroid-metabolizing enzymes and transcription factors from normal adrenal (NA), APAs and CPAs.
Design: RNA from NAs, APAs and CPAs were analyzed by microarray and real-time RT-PCR.
Setting: Academic research laboratories.
Patients: At least 9 normal controls and 12 patients with APA or CPA.
Intervention: None.
Main Outcome Measure: Expression of steroidogenic enzymes in adrenocortical disease.
Results: Microarray indicated greater than 3-fold increase in expression of CYP11B2 (aldosterone synthase) in APA while HSD11B2 (11 
-hydroxysteroid dehydrogenase type 2) and HSD17B1 (17 -hydroxysteroid dehydrogenase type 1) had greater than 3-fold increase in expression in CPA when compared with NA. Real-time RT-PCR showed that APAs produced higher levels of HSD3B2 (3-hydroxysteroid dehydrogenase type II), CYP21 (21-hydroxylase), and CYP11B2 mRNA while CPAs produced higher levels of CYP11A (cholesterol side-chain cleavage), CYP17 (17
-hydroxylase/17-20 lyase), HSD3B2 and CYP11B1 (11-hydroxylase) mRNA when compared with normal adrenal. SF-1, DAX-1 and GATA-6 were expressed at higher levels in APAs and CPAs while NURR1 was expressed at higher levels in APAs than in CPAs or NAs.
Conclusion: 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 which enhance expression of steroid-metabolizing enzymes.
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