Modulation of aldosterone and cortisol synthesis on the molecular level

Lisurek, Michael; Bernhardt, Rita

doi:10.1016/j.mce.2003.11.008

Cited by 86 publications

(58 citation statements)

References 109 publications

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“…For example, aldosterone production is regulated by both CYP11B2 expression and CYP11B2 enzyme activity. 30,32 Lisurek and Bernhardt 32 suggested that CYP11B2 enzyme activity may be post-translationally controlled by protein phosphorylation, which exerts short-term control over CYP11B2 activity. One mechanism that can be hypothesized on the N-type calcium channels in adrenocortical cells S Aritomi et al basis of these reports suggests that N-type calcium channels regulate aldosterone production by changing the activity of steroidogenic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

et al. 2010

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The inhibition of aldosterone activity is a useful approach for preventing the progression of cardiovascular and renal diseases in hypertensive patients. Although the results of our previous in vivo study suggested that N-type calcium channels may have a role in regulating plasma aldosterone levels, the direct relationship between N-type calcium channels and aldosterone production in adrenocortical cells has not been examined. In this study, the analysis of quantitative reverse transcription-PCR, western blotting, and immunocytological staining indicated the possible presence of N-type calcium channels in human adrenocortical cells (H295R cell line). Patch clamp analysis indicated that omega-conotoxin GVIA (CnTX), an N-type calcium channel inhibitor, suppressed voltage-dependent barium currents. During steroidogenesis, CnTX significantly reduced the transient calcium signaling induced by angiotensin II (Ang II) and partially prevented Ang II-induced aldosterone and cortisol formation with no significant influence on CYP11B2 and CYP11B1 mRNA expression. In addition, in a1B calcium channel subunits, knockdown significantly decreased Ang II-induced aldosterone formation with increments in CYP11B2 mRNA expression. We also investigated the inhibitory activities of some types of dihydropyridine calcium channel blockers (CCBs; cilnidipine: L-/N-type CCB, efonidipine: L-/T-type CCB, and nifedipine: L-type CCB), and these agents showed a dose-dependent inhibition effect on Ang II-induced aldosterone and cortisol production. Furthermore, only cilnidipine failed to suppress CYP11B1 expression in H295R cells. These results suggest that N-type calcium channels have a significant role in transducing the Ang II signal for aldosterone (and cortisol) biosynthesis, which may explain the mechanism by which N-type calcium channels regulate plasma aldosterone levels.

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Section: Discussionmentioning

confidence: 99%

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

et al. 2010

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“…A higher progesterone level was reported to display a delay in parturition of several days [9] . Aldosterone can sustain a homeostatic mechanism for the conservation of sodium for both mother and fetus [10] . Therefore, it can be presumed that any changes of steroid hormone level caused by xenobiotics might affect the growth and development of the fetus.…”

Section: Discussionmentioning

confidence: 99%

Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells1

Wang

Huang

Peng

et al. 2006

Acta Pharmacologica Sinica

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Aim: To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development. Methods: Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3‐methylcholanthrene, phenobarbital and dexamethasone. The activities of 7‐ethoxyresorufin O‐dealkylase, benzphetamine, aminopyrine and erythromycin N‐demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays. Results: The activities of benzphetamine and aminopyrine N‐demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25‐1 mmol/L) for 24 h. Dexamethasone (25‐100 μmol/L) also increased the activity of erythromycin N‐demethylase. The activity of 7‐ethoxyresorufin O‐dealkylase was undetected in the cells treated without and with 3‐methylcholanthrene (0.5–2 μmol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3‐methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3‐methylcholanthrene, phenobarbital or dexamethasone treatment. Conclusion: 3‐Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing‐related cytochrome P450 isoform activation.

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“…This suggests that, in IUGR males, other factors are implicated in the modulation of P450aldo activity. It could be that the electron transfer rate by the NADPHlinked redox system (adrenodoxin and adrenodoxin reductase; Lisurek & Bernhardt 2004) or the membrane composition of the mitochondria may affect mitochondrial cholesterol trafficking (Seybert 1990, Jefcoate 2002. The amount of precursors may also be responsible for these differences.…”

Section: Adrenal Changes Induced By Iugrmentioning

confidence: 99%

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

Bibeau¹,

Otis²,

St‐Louis³

et al. 2011

Journal of Endocrinology

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In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult reninangiotensin-aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT 1 R) and 2 (AT 2 R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0 . 9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT 1 R, AT 2 R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT 1 R, but increased AT 2 R mRNA while decreasing protein expression of AT 2 R and P450aldo. In males, salt intake in IUGR rats reduced both AT 1 R mRNA and protein, while for AT 2 R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT 1 R or AT 2 R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT 1 R, and AT 2 R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

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Modulation of aldosterone and cortisol synthesis on the molecular level

Cited by 86 publications

References 109 publications

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

Expression of N-type calcium channels in human adrenocortical cells and their contribution to corticosteroid synthesis

Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells1

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

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