Investigating the function of an aldosterone response pathway in primary human adrenocortical cells obtained from Conn's and phaeochromocytoma patients

Timothy J. Burton, Azizan Elena Aisha, Morris J. Brown

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The components of the classical renal aldosterone response pathway are expressed in human adrenocortical cells; however, studies in H295R cells have shown that pharmacological manipulation of this pathway has no effect on aldosterone production. We have characterised aldosterone and cortisol production by primary human adrenocortical cells and tested the hypothesis that a mineralocorticoid response pathway modulates aldosterone secretion. Aldosterone production by cells obtained from normal adrenal cortex was stimulated by angiotensin II, extracellular K + and a reduction in extracellular Na +. Conn's adenoma cells, in comparison, produced higher aldosterone/cortisol ratios and were less responsive to angiotensin II and extracellular Na +. Close coupling of aldosterone and cortisol secretion was observed in all adrenocortical cells. The mineralocorticoid receptor antagonists, eplerenone and potassium canrenoate, had no significant effect on aldosterone or cortisol production. In contrast, the glucocorticoid receptor antagonist, mifepristone, and the Na + uptake inhibitor, amiloride, had significant inhibitory effects on steroid production. Our current experiments do not support the hypothesis that an adrenal aldosterone-response pathway mediates the negative feedback of aldosterone on its own release, but do raise interest in the glucocorticoid receptor and downstream targets of the mineralocorticoid receptor as mediators of corticosteroid production.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalEuropean Journal of Pharmacology
Volume657
Issue number1-3
DOIs
Publication statusPublished - 25 Apr 2011
Externally publishedYes

Fingerprint

Pheochromocytoma
Aldosterone
Hydrocortisone
Glucocorticoid Receptors
Angiotensin II
Canrenoic Acid
Adrenocortical Adenoma
Mineralocorticoid Receptor Antagonists
Mineralocorticoid Receptors
Mifepristone
Mineralocorticoids
Amiloride
Adrenal Cortex
Adrenal Cortex Hormones
Steroids
Pharmacology
Kidney

Keywords

  • Adrenal cortex
  • Aldosterone
  • Cortisol
  • Mineralocorticoid receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Investigating the function of an aldosterone response pathway in primary human adrenocortical cells obtained from Conn's and phaeochromocytoma patients. / Burton, Timothy J.; Elena Aisha, Azizan; Brown, Morris J.

In: European Journal of Pharmacology, Vol. 657, No. 1-3, 25.04.2011, p. 184-189.

Research output: Contribution to journalArticle

@article{1529dc8ffb3a453394b974c764598323,
title = "Investigating the function of an aldosterone response pathway in primary human adrenocortical cells obtained from Conn's and phaeochromocytoma patients",
abstract = "The components of the classical renal aldosterone response pathway are expressed in human adrenocortical cells; however, studies in H295R cells have shown that pharmacological manipulation of this pathway has no effect on aldosterone production. We have characterised aldosterone and cortisol production by primary human adrenocortical cells and tested the hypothesis that a mineralocorticoid response pathway modulates aldosterone secretion. Aldosterone production by cells obtained from normal adrenal cortex was stimulated by angiotensin II, extracellular K + and a reduction in extracellular Na +. Conn's adenoma cells, in comparison, produced higher aldosterone/cortisol ratios and were less responsive to angiotensin II and extracellular Na +. Close coupling of aldosterone and cortisol secretion was observed in all adrenocortical cells. The mineralocorticoid receptor antagonists, eplerenone and potassium canrenoate, had no significant effect on aldosterone or cortisol production. In contrast, the glucocorticoid receptor antagonist, mifepristone, and the Na + uptake inhibitor, amiloride, had significant inhibitory effects on steroid production. Our current experiments do not support the hypothesis that an adrenal aldosterone-response pathway mediates the negative feedback of aldosterone on its own release, but do raise interest in the glucocorticoid receptor and downstream targets of the mineralocorticoid receptor as mediators of corticosteroid production.",
keywords = "Adrenal cortex, Aldosterone, Cortisol, Mineralocorticoid receptor",
author = "Burton, {Timothy J.} and {Elena Aisha}, Azizan and Brown, {Morris J.}",
year = "2011",
month = "4",
day = "25",
doi = "10.1016/j.ejphar.2011.01.051",
language = "English",
volume = "657",
pages = "184--189",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Investigating the function of an aldosterone response pathway in primary human adrenocortical cells obtained from Conn's and phaeochromocytoma patients

AU - Burton, Timothy J.

AU - Elena Aisha, Azizan

AU - Brown, Morris J.

PY - 2011/4/25

Y1 - 2011/4/25

N2 - The components of the classical renal aldosterone response pathway are expressed in human adrenocortical cells; however, studies in H295R cells have shown that pharmacological manipulation of this pathway has no effect on aldosterone production. We have characterised aldosterone and cortisol production by primary human adrenocortical cells and tested the hypothesis that a mineralocorticoid response pathway modulates aldosterone secretion. Aldosterone production by cells obtained from normal adrenal cortex was stimulated by angiotensin II, extracellular K + and a reduction in extracellular Na +. Conn's adenoma cells, in comparison, produced higher aldosterone/cortisol ratios and were less responsive to angiotensin II and extracellular Na +. Close coupling of aldosterone and cortisol secretion was observed in all adrenocortical cells. The mineralocorticoid receptor antagonists, eplerenone and potassium canrenoate, had no significant effect on aldosterone or cortisol production. In contrast, the glucocorticoid receptor antagonist, mifepristone, and the Na + uptake inhibitor, amiloride, had significant inhibitory effects on steroid production. Our current experiments do not support the hypothesis that an adrenal aldosterone-response pathway mediates the negative feedback of aldosterone on its own release, but do raise interest in the glucocorticoid receptor and downstream targets of the mineralocorticoid receptor as mediators of corticosteroid production.

AB - The components of the classical renal aldosterone response pathway are expressed in human adrenocortical cells; however, studies in H295R cells have shown that pharmacological manipulation of this pathway has no effect on aldosterone production. We have characterised aldosterone and cortisol production by primary human adrenocortical cells and tested the hypothesis that a mineralocorticoid response pathway modulates aldosterone secretion. Aldosterone production by cells obtained from normal adrenal cortex was stimulated by angiotensin II, extracellular K + and a reduction in extracellular Na +. Conn's adenoma cells, in comparison, produced higher aldosterone/cortisol ratios and were less responsive to angiotensin II and extracellular Na +. Close coupling of aldosterone and cortisol secretion was observed in all adrenocortical cells. The mineralocorticoid receptor antagonists, eplerenone and potassium canrenoate, had no significant effect on aldosterone or cortisol production. In contrast, the glucocorticoid receptor antagonist, mifepristone, and the Na + uptake inhibitor, amiloride, had significant inhibitory effects on steroid production. Our current experiments do not support the hypothesis that an adrenal aldosterone-response pathway mediates the negative feedback of aldosterone on its own release, but do raise interest in the glucocorticoid receptor and downstream targets of the mineralocorticoid receptor as mediators of corticosteroid production.

KW - Adrenal cortex

KW - Aldosterone

KW - Cortisol

KW - Mineralocorticoid receptor

UR - http://www.scopus.com/inward/record.url?scp=79952487209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952487209&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2011.01.051

DO - 10.1016/j.ejphar.2011.01.051

M3 - Article

VL - 657

SP - 184

EP - 189

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -