title: Aldosterone-producing adenoma formation in the adrenal cortex involves expression of stem/progenitor cell markers.
abstract: Aldosterone producing adenoma (APA) is the most common form of surgically curable hypertension. To further understand mechanisms involved in APA formation, we investigated the expression of molecules linked to adrenal stem/precursor cells [β-catenin, Sonic hedgehog (Shh), CD56], and nuclear receptors that play key roles in adrenocortical development and function steroidogenic factor 1, dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1) in six control adrenal glands and 14 adrenals with APA and compared their expression with that of specific markers of zona glomerulosa (ZG) [CYP11B2, Disabled 2 (Dab2)]. Both Dab2 and CD56 were expressed in ZG. Although Dab2 associates uniquely with differentiated ZG cells and its expression is lost when cells transdifferentiate to zona fasciculata (ZF) cells, CD56 was also expressed in ZF and in aldosterone-producing cell clusters, confirming that these structures possess an intermediate phenotype between ZG and ZF cells. Shh was barely detectable in cells located to the outer part of the ZG in the control adrenal; in contrast, its expression was detected in the entire APA and was dramatically increased in the hyperplastic peritumoral ZG. Transcriptome profiling revealed differential expression of components of Shh signaling pathway in a subgroup of APA. Similarly, Wnt/β-catenin signaling was activated in the majority of APA as well as in the entire peritumoral adrenal cortex; however, no mutation was identified in the CTNNB1 gene that could account for β-catenin activation. Our data suggest that both APA and adjacent ZG present characteristics of stem/precursor cells; the reexpression of genes involved in fetal adrenal development could underlie excessive ZG cell proliferation and APA formation.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 970, PARCC, 56 Rue Leblanc, 75015 Paris, France. sheerazed.boulkroun@inserm.fr
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
authors.forename: Benoit
authors.initials: B
authors.lastname: Samson-Couterie
authors.forename: José-Felipe
authors.initials: JF
authors.lastname: Golib-Dzib
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: Tchao
authors.initials: T
authors.lastname: Meatchi
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology*; D000311:Adrenal Glands / Q000473:pathology; D000450:Aldosterone; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension; D066298:In Vitro Techniques; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D015384:Zona Glomerulosa
chemical_list: D015415:Biomarkers; D000450:Aldosterone