Aldosterone production in human adrenocortical cells is stimulated by high-density lipoprotein 2 (HDL2) through increased expression of aldosterone synthase (CYP11B2).
Adrenal aldosterone production is regulated by physiological agonists at the level of early and late rate-limiting steps. Numerous studies have focused on the role of lipoproteins including high-density lipoprotein (HDL) as cholesterol providers in this process; however, recent research suggests that HDL can also act as a signaling molecule. Herein, we used the human H295R adrenocortical cell model to study the effects of HDL on adrenal aldosterone production and CYP11B2 expression. HDL, especially HDL2, stimulated aldosterone synthesis by increasing expression of CYP11B2. HDL treatment increased CYP11B2 mRNA in both a concentration- and time-dependent manner, with a maximal 19-fold increase (24 h, 250 μg/ml of HDL). Effects of HDL on CYP11B2 were not additive with natural agonists including angiotensin II or K(+). HDL effects were likely mediated by a calcium signaling cascade, because a calcium channel blocker and a calmodulin kinase inhibitor abolished the CYP11B2-stimulating effects. Of the two subfractions of HDL, HDL2 was more potent than HDL3 in stimulating aldosterone and CYP11B2. Further studies are needed to identify the active components of HDL, which regulate aldosterone production.
Department of Physiology, Medical College of Georgia, 1120 15th Street, CA-3094, Augusta, Georgia 30912, USA.
Yewei
Y
Xing
Anthony
A
Cohen
George
G
Rothblat
Sandhya
S
Sankaranarayanan
Ginny
G
Weibel
Lori
L
Royer
Omar L
OL
Francone
William E
WE
Rainey
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D008076:Cholesterol, HDL / Q000494:pharmacology*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism
D008076:Cholesterol, HDL; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D002118:Calcium
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