Angiotensin II regulation of adrenocortical gene transcription

Nogueira, Edson; Bollag, Wendy B.; Rainey, William E.

doi:10.1016/j.mce.2008.08.024

Cited by 52 publications

(40 citation statements)

References 92 publications

(97 reference statements)

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“…2) (14, 32-35). Not all steroidogenic enzymes were increased upon AngII stimulation (11). Moreover, the expression profiles were time dependent.…”

Section: Resultsmentioning

confidence: 91%

“…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)(11)(12): (i) an early (within minutes after stimulation) upregulation of aldosterone synthesis through posttranslational activation of steroidogenic acute regulatory (StAR) protein that facilitates the transfer of cholesterol (steroid precursor) to the mitochondria and (ii) a relatively late (hours after stimulation) enhancement of aldosterone synthesis by increasing the capacity to produce aldosterone through increased expression of relevant enzymes in ZG cells. It has been well documented that AngII triggers expression of CYP11B2 (aldosterone synthase), an enzyme also known to be expressed specifically within ZG cells.…”

mentioning

confidence: 99%

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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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“…2) (14, 32-35). Not all steroidogenic enzymes were increased upon AngII stimulation (11). Moreover, the expression profiles were time dependent.…”

Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 99%

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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“…Adrenal glands seems able to produce renin, and consequently Ang II, in a kidney-independent way [93]. All components of the RAAS are present in adrenal cortex and comprise the adrenal RAAS.…”

Section: Raas Overviewmentioning

confidence: 99%

“…All components of the RAAS are present in adrenal cortex and comprise the adrenal RAAS. Renin and angiotensinogen mRNA have been identified in the adrenal gland, and Ang II formation has been demonstrated in zona glomerulosa cells.7 Most (90%) adrenal renin activity has been localized to the zona glomerulosa, [93] and more than 90% of adrenal Ang II originates at local tissue sites. [94] In transgenic animal models it has been shown that sodium restriction can increase adrenal renin and aldosterone independently of plasma or kidney renin concentrations.…”

Section: Raas Overviewmentioning

confidence: 99%

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Raimondo¹,

Tuttolomondo²,

Buttà³

et al. 2012

CPD

106

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Abstract:The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosteron system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Recpetor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflmmatory effect of drugs bocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

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“…Romero et al, Nogueira et al, and others reported that on adrenal cortex and aldosterone-related research the mRNA variations in vitro are expected to reflect what happens in vivo [22,25,26,28,[36][37][38], and thus, it is considered that AII and FSK may control MT-3 protein levels in adrenocortical tissues. FSK is known to induce the cAMP pathway, leading to an increase in CYP11B1/B2 expression levels with subsequent corticosteroid production in the adrenal cortex [37], while AII activates phospholipase C through G protein subunit q/11 (G q/11 ), as well as several other signaling molecules, including protein kinase C, calcium/calmodulin-dependent kinases, mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1 and 2 (MEK1/2-ERK1/2), src-family kinases, ras/raf kinases (RAS/RAF), and Janus kinase (JAK)/signal transduction and activators of transcription [38]. These intricate pathways and numerous regulatory factors indicate that any possible mechanisms by which MT-3 may act under the influence of cAMP or AII are rather complex processes and should require further research for clarification.…”

Section: Discussionmentioning

confidence: 99%

Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

et al. 2013

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Metallothionein-3 (MT-3) is an intracellular, low molecular weight protein mainly distributed in the central nervous system but also in various peripheral organs and several types of human neoplasms. However, details of MT-3 expression have not been examined in human adrenal cortex and its disorders. The mRNA levels of MT-3 were first evaluated by quantitative RT-PCR (qPCR) in adrenocortical aldosterone-producing adenoma (APA: 11) and cortisol-producing adenoma (CPA: 14). In addition, MT-3 immunohistochemistry was performed in non-pathological adrenal glands (NA: 19), idiopathic hyperaldosteronism (IHA: 10), APA (20), CPA (24), adjacent non-neoplastic adrenal glands of adenoma (AAG: 20), and adrenocortical carcinoma (ACC: 8). H295R cells were also treated with angiotensin-II or forskolin in a time-dependent manner, and the changes of MT-3 mRNA levels were evaluated by qPCR. Results of qPCR analysis demonstrated that MT-3 mRNA levels were significantly higher in APA than CPA (P = 0.0004). MT-3 immunoreactivity was detected in the zona glomerulosa of NA, IHA, and AAG, as well as in APA, CPA, and ACC. When treated with angiotensin-II and forskolin, MT-3 mRNA levels reached a peak by 12 h in H295R cells, with significantly higher levels compared to control non-treated cells (P < 0.01). The presence of MT-3 in the ZG of NA, IHA, and AAG, as well as APA may imply a role in the pathophysiology of aldosterone-producing tissues.

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Angiotensin II regulation of adrenocortical gene transcription

Cited by 52 publications

References 92 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

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

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