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Submitted on June 10, 2005
Accepted on November 30, 2005
University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology (K.S.A, B.A.M) and Department of Pediatrics (P.C.W), Dallas, Texas 75390-9032; University of Padua, Department of Medical and Surgery Sciences, Padua, Italy (F.M., F.S.); University of Louisville Health Sciences Center, Department of Obstetrics and Gynecology and Women's Health, Louisville, Kentucky 40292 (C.V.R). Medical College of Georgia, Department of Physiology, Augusta, Georgia 30912
* To whom correspondence should be addressed. E-mail: wrainey{at}mcg.edu.
Context: The mechanisms driving steroid production in aldosterone-producing adenomas are poorly defined. However, previous studies have shown that steroid production in some cortisol-producing adenomas is regulated by aberrant expression of G protein-coupled receptors. Aberrant adrenal expression of LH receptors has been shown to cause Cushing's syndrome, but the role of LH receptors in Conn's disease (hyperaldosteronism) has not been studied.
Objective: To determine if aldosterone-producing adenomas (APA) express elevated LH receptor compared with normal adrenal.
Design: Pools of RNA from normal adrenal (NA) and APAs were hybridized to oligonucleotide microarrays. Data were confirmed using real-time RTPCR analysis of RNA derived from NA (n = 20) and APAs (n = 18). Aldosterone synthase transcription was studied in H295R adrenocortical cells transfected with an LHR expression construct and reporter constructs prepared from CYP11B2 5'-flanking DNA.
Patients: Twenty normal control adrenals and 18 adenomas from patients with aldosterone-producing adenomas.
Main Outcome Measure: Regulation of CYP11B2 gene expression by aberrant LH receptor expression in aldosterone-producing adrenal adenoma.
Results: LHCGR and CYP11B2 are indicated as having greater than 25-fold expression in one pool of APA mRNA samples over normal adrenal using microarray analysis. Real-time RTPCR analyses indicated one APA sample (LHR-APA) exhibited >2400-fold elevation in LHR expression over NA. Examination of LHR mRNA levels in 18 independent APA samples indicated elevated expression in 9 samples when compared with NA. In H295R cells transfected with LH receptor, LH treatment caused a concentration-dependent increase in CYP11B2 reporter activity.
Conclusion: LH receptor expression is elevated in many aldosterone-producing adenomas, which makes LH a potential cause of the excessive production of aldosterone in a subset of these adrenal tumors.
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