Characterization and regulation of the angiotensin II type‐1 receptor (binding and mRNA) in human adrenal fasciculata‐reticularis cells

Naville, Danielle; Lebrethon, Marie-Christine; Kermabon, A.Y.; Rouer, Évelyne; Bénarous, Richard; Saez, J.M.

doi:10.1016/0014-5793(93)80104-3

Cited by 45 publications

(18 citation statements)

References 28 publications

(7 reference statements)

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“…We also show that Ang II-induced aldosterone release could be totally blocked by losartan, indicating that Ang II is physiologically active in NCI-H295 cells by stimulation of an AT 1 receptor, as it has been previously demonstrated in this cell line and in human and rat adrenocortical cells. 9,26,27 The expression of AT 1 receptors and not AT 2 receptors could be confirmed by binding studies.…”

Section: Discussionmentioning

confidence: 71%

Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

et al. 1999

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Abstract-NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system to define the role of the renin-angiotensin system in the regulation of aldosterone production in humans. Because the precise cellular localization of the components of the renin-angiotensin system in human adrenal cortical cells remains unclear, we investigated their localization in this defined cell system. NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse transcriptase polymerase chain reaction and immunohistochemistry. Human angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry, ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5 mmol/L K ϩ stimulated the formation of both angiotensin I and angiotensin II 1.9-and 2.5-fold, respectively, and increased aldosterone release 3.0-fold. The K ϩ -induced stimulation of aldosterone release was decreased by captopril and enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT 1 )-receptor antagonist losartan (28%). Key Words: NCI-H295 cell line Ⅲ renin-angiotensin system Ⅲ angiotensin II Ⅲ aldosterone Ⅲ potassium T he renin-angiotensin-system (RAS) plays an important role in the regulation of blood pressure as well as sodium and volume homeostasis. 1 In addition to the circulating RAS, local RAS have been documented in a number of animal and human tissues including the adrenal gland (for review, see Reference 2 ). In the adrenal cortex, the role of the local RAS has not been fully characterized. [3][4][5] The human adrenal zona glomerulosa expresses all the components of the RAS, including angiotensinogen (AOG), renin, and angiotensinconverting enzyme (ACE) 2,5 as well as the prohormone convertase PC5 mRNA. 6 Locally produced angiotensin II (Ang II) has been proposed to exercise an autocrine/paracrine control of aldosterone secretion. 2 In many tissues, the various components of the RAS are found in different cells, 7 and it is not clear whether the components of the adrenocortical RAS are produced by different cells or if one cell contains all components. Precise data on the localization and regulation of the RAS components are a requirement for the investigation and interpretation of this system. The examination of an isolated adrenal RAS is especially important to differentiate between the effects caused by circulating and local adrenal systems.The human adrenocortical carcinoma cell line NCI-H295 is a widely accepted model for human adrenocortical studies. This cell line, originally cultured from a human adrenocortical tumor in 1980, represents the first cell line to maintain the ability to produce all adrenocortical steroids, expressing the 3 major pathways of adrenal steroidogenesis including the main steroidogenic enzymes. 8 As in normal human adrenocortical cells, synthesis of aldosterone is regulated by Ang II through AT 1 receptors 9,10 and potassium. 11 These cells therefore may be a suitable system for the characterization of a local RAS.

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Section: Discussionmentioning

confidence: 71%

Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

et al. 1999

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“…Moreover, these cells contain AT 1 receptor subtype and express AT1 receptor mRNA, and both receptor number and mRNA are negatively regulated by A-Il ( 18). Further evidence indicating that HAC are a target for A-II was given by the fact that the hormone increases the ACTH receptor mRNA levels in a dose-dependent manner, and that these effects are mediated mainly via transcriptional mechanisms.…”

Section: Resultsmentioning

confidence: 99%

Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

Lebrethon¹,

Naville²,

Bégeot³

et al. 1994

J. Clin. Invest.

142

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The regulation of ACIH receptor binding sites and mRNA by ACIH and angiotensin II (A-II) was studied using cultured human adrenal fasciculatareticularis cells (HAC). These cells expressed two major ACTH receptor transcripts of 1.8 and 3.4 kb and three minor ones of4, 7, and 11 kb. ACTH increased the levels of all these transcripts in a time-and dose-dependent manner. At a maximal concentration of 10-8 M, ACTH enhanced 21-and 4-fold the level of ACTH receptor mRNA and the number of receptors per cell, respectively. Pretreatment of HAC with A-II produced a dose-dependent enhancement of ACTH receptor mRNA that was associated with an increase of both ACJ7H receptor number and responsiveness to this hormone. The effects of A-II were completely blocked by an AT1 receptor subtype antagonist but not by an AT2 antagonist. The effects of ACTH together with A-II on ACJH receptor mRNA were greater than those induced by each hormone alone. These results show that ACTH receptor number and mRNA are positively regulated by the two main hormones (ACTH and A-II) which, in vivo, regulate adrenocortical functions. In addition, they also show that HAC are a target for A-II. Thus, regulation of ACTH receptors may be one mechanism by which AC'H and A-II regulate adrenocortical functions under both normal and pathological conditions. (J. Clin. Invest. 1994. 93:1828-1833

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“…Ang II stimulates glucocorticoid release by enhancing the CRH-mediated ACTH release (Gaillard et al 1981, 1985, Abou-Samra et al 1986, Schoenenberg et al 1987 or by stimulating adrenal glucocorticoid production (Naville et al 1993). We recently demonstrated that Ang II increased the corticosterone responsiveness to CRH, an effect that was associated with an upregulation of the AT 1A receptor (Müller et al 2007).…”

Section: Discussionmentioning

confidence: 97%

“…Over the last few years, it has been established that angiotensin II (Ang II) AT receptors (AGTR as listed in the MGI Database) are present in the organs of the hypothalamopituitary-adrenal (HPA) axis (Burson et al 1994, Gasc et al 1994, Llorens-Cortes et al 1994, Jöhren et al 1995, Jöhren & Saavedra 1996, that they are regulated during stress (Castren & Saavedra 1988, Aguilera et al 1995, Leong et al 2002, and that Ang II influences HPA axis reactivity by enhancing the synthesis and secretion of CRH, ACTH, and glucocorticoids (Rivier & Vale 1983, Abou-Samra et al 1986, Schoenenberg et al 1987, Sumitomo et al 1991, Naville et al 1993, Jezova et al 1998. This crosstalk between the renin-angiotensinaldosterone system (RAAS) and the HPA axis is functionally relevant for hypertension.…”

Section: Introductionmentioning

confidence: 99%

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

Müller

Kröger²,

Szymczak³

et al. 2009

Journal of Endocrinology

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AT 1 blockers attenuate hypothalamo-pituitary-adrenal (HPA) axis reactivity in hypertension independently of their potency to lower blood pressure. A reduced pituitary sensitivity to CRH and a downregulation of hypothalamic CRH expression have been suggested to influence HPA axis activity during chronic AT 1 blockade. This study was aimed at confirming the role of central angiotensin II in regulating HPA reactivity by using the transgenic rat TGR(ASrAO-GEN), a model featuring low levels of brain angiotensinogen. Different stress tests were performed to determine HPA reactivity in TGR(ASrAOGEN) and appropriate controls. In TGR(ASrAOGEN), blood pressure was diminished compared to controls. The corticosterone response to a CRH or ACTH challenge and a forced swim test was more distinct in TGR(ASrAOGEN) than it was in controls and occurred independently of a concurrent enhancement in ACTH. Using quantitative real-time PCR, we found increased mRNA levels of melanocortin 2 (Mc2r) and AT 2 receptors (Agtr2) in the adrenals of TGR(ASrAOGEN), whereas mRNA levels of Crh, Pomc, and AT 1 receptors (Agtr1) remained unchanged in hypothalami and pituitary glands. Since stress responses were increased rather than attenuated in TGR(ASrAOGEN), we conclude that the reduced HPA reactivity during AT 1 blockade could not be mimicked in a specific transgenic rat model featuring a centrally inactivated renin-angiotensin-aldosterone system. The ACTH independency of the enhanced corticosterone release during CRH test and the enhanced corticosterone response to ACTH rather indicates an adrenal mechanism. The upregulation of adrenal MC2 and AT 2 receptors seems to be involved in the stimulated facilitation of adrenal corticosterone release for effectuating the stimulated stress responses.

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Characterization and regulation of the angiotensin II type‐1 receptor (binding and mRNA) in human adrenal fasciculata‐reticularis cells

Cited by 45 publications

References 28 publications

Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

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Characterization and regulation of the angiotensin II type‐1 receptor (binding and mRNA) in human adrenal fasciculata‐reticularis cells

Cited by 45 publications

References 28 publications

Local Renin-Angiotensin System Is Involved in K + -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Local Renin-Angiotensin System Is Involved in K + -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

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Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells

Local Renin-Angiotensin System Is Involved in K ⁺ -Induced Aldosterone Secretion from Human Adrenocortical NCI-H295 Cells