Aberrant hormone receptors in primary aldosteronism.
The mechanisms involved in the renin-independent regulation of aldosterone secretion in primary aldosteronism are poorly understood. In ACTH-independent Cushing's syndrome, cortisol secretion can be regulated by the aberrant expression of G-protein coupled receptors (GPCRs) in unilateral tumors and bilateral macronodular adrenal hyperplasia. By analogy, some recent studies identified overexpression or function of several GPCR as a potential cause for excess aldosterone production in some aldosteronomas and in bilateral idiopathic hyperaldosteronism. Initial studies have used in vitro techniques, while the clinical aldosterone responses were not assessed. More recently, several receptors have been shown to be expressed in aldosterone-producing adrenal tumors in vitro and to regulate aberrantly renin-independent aldosterone secretion in vivo. The prevalence of aberrant hormone receptors in primary aldosteronism could be elevated, but larger systematic studies are required to establish its true frequency. The identification of aberrant adrenal GPCRs by in vivo functional studies offers the potential for novel pharmacological therapies that either suppress the endogenous ligands or block the receptor with specific antagonists.
Mazzuco
T L
TL
Division of Endocrinology, Department of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montréal, Canada.
Grunenwald
S
S
Lampron
A
A
Bourdeau
I
I
Lacroix
A
A
D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
D050505:Mutant Proteins; D018043:Receptors, Corticotropin; D043562:Receptors, G-Protein-Coupled; D000450:Aldosterone