Role of angiotensin II-induced rapid response genes in the regulation of enzymes needed for aldosterone synthesis

Nogueira, Edson; Xing, Yewei; Morris, Claudia A V; Rainey, William E.

doi:10.1677/jme-08-0112

Cited by 58 publications

(51 citation statements)

References 72 publications

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“…7A and B for mRNA and protein, respectively). In agreement with the previously described role for the NGFIB family in CYP11B2 expression (19)(20)(21)(22), knockdown of NGFIB and NURR1 decreased AngIIstimulated induction of CYP11B2 (Fig. 7C, right).…”

Section: From H295r Cells After 3 H Of Incubation With Angii or Vehicsupporting

confidence: 92%

“…After recovery for 24 h, cells were lysed, and luciferase activity was measured. previous study (20) (also see Discussion). Finally, we also confirmed that HSD3B2 was not responsive to AngII, irrespective of the presence of DN-NGFIB.…”

Section: From H295r Cells After 3 H Of Incubation With Angii or Vehicsupporting

confidence: 70%

“…Our data also provide evidence that the acute induction of HSD3B1 is fully dependent on AngIIstimulated de novo protein synthesis of the orphan nuclear receptors NGFIB and NURR1. Interestingly, the NGFIB protein family has been implicated in the regulation of CYP11B2 as well (19)(20)(21)(22). However, we found that the regulation of this gene is not entirely dependent on de novo protein synthesis.…”

mentioning

confidence: 61%

“…These common responses of NGFIB family members across different species suggest that the AngII induction of these transcription factors may be necessary for the coordinate regulation of steroid synthesis. Consistent with this hypothesis, Nogueira et al previously demonstrated that overexpression of a dominant negative NGFIB mutant causes a significant reduction of aldosterone synthesis in AngII-stimulated H295R cells (20). However, probably because NGFIB family members have redundant roles, prior studies using targeted disruption of individual family members have not found adrenal phenotypes (53,54).…”

Section: Discussionmentioning

confidence: 86%

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Angiotensin II Triggers Expression of the Adrenal Gland Zona Glomerulosa-Specific 3β-Hydroxysteroid Dehydrogenase Isoenzyme through De Novo Protein Synthesis of the Orphan Nuclear Receptors NGFIB and NURR1

Ota

Doi

Yamazaki

et al. 2014

Molecular and Cellular Biology

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The 3␤-hydroxysteroid dehydrogenase (3␤-HSD) is an enzyme crucial for steroid synthesis. Two different 3␤-HSD isoforms exist in humans. Classically, HSD3B2 was considered the principal isoform present in the adrenal. However, we recently showed that the alternative isoform, HSD3B1, is expressed specifically within the adrenal zona glomerulosa (ZG), where aldosterone is produced, raising the question of why this isozyme needs to be expressed in this cell type. Here we show that in both human and mouse, expression of the ZG isoform 3␤-HSD is rapidly induced upon angiotensin II (AngII) stimulation. AngII is the key peptide hormone regulating the capacity of aldosterone synthesis. Using the human adrenocortical H295R cells as a model system, we show that the ZG isoform HSD3B1 differs from HSD3B2 in the ability to respond to AngII. Mechanistically, the induction of HSD3B1 involves de novo protein synthesis of the nuclear orphan receptors NGFIB and NURR1. The HSD3B1 promoter contains a functional NGFIB/NURR1-responsive element to which these proteins bind in response to AngII. Knockdown of these proteins and overexpression of a dominant negative NGFIB both reduce the AngII responsiveness of HSD3B1. Thus, the AngII-NGFIB/NURR1 pathway controls HSD3B1. Our work reveals HSD3B1 as a new regulatory target of AngII.T he enzyme 3␤-hydroxysteroid dehydrogenase/⌬ 5 -⌬ 4 -isomerase (3␤-HSD) is essential for the biosynthesis of all active steroid hormones, including those secreted from the adrenal gland (1-4). Whereas two distinct 3␤-HSD isoforms (type I 3␤-HSD, which is encoded by HSD3B1, and type II 3␤-HSD, which is encoded by HSD3B2) exist in humans, it has long been thought that type II 3␤-HSD was the only isoform expressed in the human adrenal glands (1). However, this canonical view was recently revised due to the observation that the alternative isoform, HSD3B1, is expressed within zona glomerulosa (ZG) cells (5, 6), where aldosterone is produced. Interestingly, the mouse also has two isoforms in the adrenal: one (Hsd3b1) is ubiquitous in the cortex, but the other (Hsd3b6) is ZG specific (6-9). Thus, in both species, the adrenals possess a ZG-specific isoform, in addition to the ubiquitous one. However, it remains unknown why these different enzymes are expressed simultaneously in ZG cells. Since these isozymes catalyze the same enzymatic reaction, the question remains open why the newly identified ZG-specific isoform needs to be expressed in ZG cells.Angiotensin II (AngII) is the key peptide hormone in the renin-angiotensin-aldosterone system (RAAS). AngII is a potent secretagogue of the mineralocorticoid aldosterone, which is principally synthesized within the adrenal gland ZG cells through a series of enzymatic reactions that involve multiple enzymes, including 3␤-HSDs. The actions of AngII on ZG cells are often divided into two temporally different phases (10-12): (i) an early (within minutes after stimulation) upregulation of aldosterone synthesis through posttranslational activation of steroidogenic acute regulatory...

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Section: From H295r Cells After 3 H Of Incubation With Angii or Vehicsupporting

confidence: 92%

Section: From H295r Cells After 3 H Of Incubation With Angii or Vehicsupporting

confidence: 70%

mentioning

confidence: 61%

Section: Discussionmentioning

confidence: 86%

See 2 more Smart Citations

Angiotensin II Triggers Expression of the Adrenal Gland Zona Glomerulosa-Specific 3β-Hydroxysteroid Dehydrogenase Isoenzyme through De Novo Protein Synthesis of the Orphan Nuclear Receptors NGFIB and NURR1

Ota

Doi

Yamazaki

et al. 2014

Molecular and Cellular Biology

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“…31 Further, the binding of Ang II to AT1R enhances the activity of SRC and protein kinase C (PKC), which upregulates CYP11B2. 32, 33 Although many studies in animals, cells, and human populations have implicated SRC and CSK in blood pressure regulation, the mechanisms through which this occurs has not been determined. We have reported that knockdown and haploinsufficiency of Csk increase blood pressure through Src.…”

Section: Animal Research and Ethics Statementmentioning

confidence: 99%

Csk Regulates Blood Pressure by Controlling the Synthetic Pathways of Aldosterone

Kim

Kang

Lim

et al. 2018

Circ J

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represent extreme cases, because most hypertensive cases are not explained by a mutation in a single gene. 3 Further, the finding of genes that cause monogenic syndromes highlights the significant functions of the kidney and adrenal gland in regulating blood pressure. 2,3 Specifically, 10% of all monogenic forms of hypertension are estimated to have primary aldosteronism, suggesting that the homeostatic maintenance of aldosterone levels and the effect of aldosterone on kidney function are pivotal in keeping blood pressure within the normal range. 3 Despite the increase in the discoveries of SNPs that are associated with blood pressure, few cases have revealed an association between a genetic variation and the causal pathway that leads to hypertension. The most notable studies have reported a variant (rs13333226) in the promoter region of the uromodulin gene (UMOD), 8 a SNP in the promoter (rs3918226) near the endothelial nitric oxide synthase (eNOS) gene, 9,10 a SNP (rs5068) in the 3' untranslated region of NPPA, the gene that encodes for atrial natriuretic peptide (ANP), 11,12 and a SNP (rs17249754) B lood pressure is a complex trait that is regulated by a network of physiological pathways that involve the modulation of heart rate, vascular tone, and blood volume. 1 Short-term regulation of blood pressure is attained via the effects of sympathetic/parasympathetic activation on vascular tone and cardiac contractility through the sensing of baroreceptors in large arteries, whereas longterm regulation occurs through the effects of the reninangiotensin-aldosterone system (RAAS) on the kidney in controlling blood volume. 2 Despite their classical definition, short-term regulatory mechanisms are not easily dissected from long-term mechanisms, because the autonomic nervous system and RAAS permeate common target tissues and often relay signals through shared signaling pathways.Genetic research, including genome-wide association studies (GWASs), has identified approximately 116 singlenucleotide polymorphisms (SNPs) and rare mutations that contribute to the genetic architecture of blood pressure and hypertension. 3-7 It is now evident that hypertension is a polygenic trait, wherein rare syndromes of hypertension Background: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported that Csk insufficiency increases blood pressure through Src. The mechanisms of hypertension in Csk +/− mice are examined further in this study.

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Regulation of Aldosterone Synthesis and Secretion

Bollag

2014

Comprehensive Physiology

154

110

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Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone is responsible for regulating sodium homeostasis, thereby helping to control blood volume and blood pressure. Insufficient aldosterone secretion can lead to hypotension and circulatory shock, particularly in infancy. On the other hand, excessive aldosterone levels, or those too high for sodium status, can cause hypertension and exacerbate the effects of high blood pressure on multiple organs, contributing to renal disease, stroke, visual loss, and congestive heart failure. Aldosterone is also thought to directly induce end-organ damage, including in the kidneys and heart. Because of the significance of aldosterone to the physiology and pathophysiology of the cardiovascular system, it is important to understand the regulation of its biosynthesis and secretion from the adrenal cortex. Herein, the mechanisms regulating aldosterone production in zona glomerulosa cells are discussed, with a particular emphasis on signaling pathways involved in the secretory response to the main controllers of aldosterone production, the renin-angiotensin II system, serum potassium levels and adrenocorticotrophic hormone. The signaling pathways involved include phospholipase C-mediated phosphoinositide hydrolysis, inositol 1,4,5-trisphosphate, cytosolic calcium levels, calcium influx pathways, calcium/calmodulin-dependent protein kinases, diacylglycerol, protein kinases C and D, 12-hydroxyeicostetraenoic acid, phospholipase D, mitogen-activated protein kinase pathways, tyrosine kinases, adenylate cyclase, and cAMP-dependent protein kinase. A complete understanding of the signaling events regulating aldosterone biosynthesis may allow the identification of novel targets for therapeutic interventions in hypertension, primary aldosteronism, congestive heart failure, renal disease, and other cardiovascular disorders.

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Role of angiotensin II-induced rapid response genes in the regulation of enzymes needed for aldosterone synthesis

Cited by 58 publications

References 72 publications

Angiotensin II Triggers Expression of the Adrenal Gland Zona Glomerulosa-Specific 3β-Hydroxysteroid Dehydrogenase Isoenzyme through De Novo Protein Synthesis of the Orphan Nuclear Receptors NGFIB and NURR1

Angiotensin II Triggers Expression of the Adrenal Gland Zona Glomerulosa-Specific 3β-Hydroxysteroid Dehydrogenase Isoenzyme through De Novo Protein Synthesis of the Orphan Nuclear Receptors NGFIB and NURR1

Csk Regulates Blood Pressure by Controlling the Synthetic Pathways of Aldosterone

Regulation of Aldosterone Synthesis and Secretion

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