Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas.
BACKGROUND
The mechanisms driving steroid production in aldosterone-producing adenomas (APAs) 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
The objective of the study was to determine whether APAs express elevated LH receptor, compared with normal adrenal (NA).


METHODS
Pools of RNA from NA and APAs were hybridized to oligonucleotide microarrays. Data were confirmed using real-time RT-PCR analysis of RNA derived from NA (n = 20) and APAs (n = 18). Aldosterone synthase transcription was studied in H295R adrenocortical cells transfected with an LH receptor expression construct and reporter constructs prepared from CYP11B2 5'-flanking DNA.


METHODS
The patient population consisted of 20 normal control adrenals and 18 adenomas from patients with APAs.


METHODS
Regulation of CYP11B2 gene expression by aberrant LH receptor expression in aldosterone-producing adrenal adenoma was measured.


RESULTS
LH/choriogonadotropin receptor gene and CYP11B2 are indicated as having greater than 25-fold expression in one pool of APA mRNA samples over NA using microarray analysis. Real-time RT-PCR analyses indicated that one APA sample (APA-LH receptor) exhibited more than 2400-fold elevation in LH receptor expression over NA. Examination of LH receptor mRNA levels in 18 independent APA samples indicated elevated expression in nine samples when compared with NA. In H295R cells transfected with LH receptor, LH treatment caused a concentration-dependent increase in CYP11B2 reporter activity.


CONCLUSIONS
LH receptor expression is elevated in many APAs, which makes LH a potential cause of the excessive production of aldosterone in a subset of these adrenal tumors.
Saner-Amigh
Karla
K
Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
Mayhew
Bobbie A
BA
Mantero
Franco
F
Schiavi
Francesca
F
White
Perrin C
PC
Rao
Chalama V
CV
Rainey
William E
WE
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D000311:Adrenal Glands / Q000196:embryology / Q000502:physiology; D000450:Aldosterone / Q000378:metabolism*; D003338:Corpus Luteum / Q000502:physiology; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D006080:Ovarian Follicle / Q000502:physiology; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D011974:Receptors, LH; D000450:Aldosterone