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Horm Metab Res 2009; 41(1): 35-39
DOI: 10.1055/s-0028-1087188
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Contrasting Effects of Eplerenone and Spironolactone on Adrenal Cell Steroidogenesis

P. Ye 1 , T. Yamashita 2 , D. M. Pollock 3 , H. Sasano 2 , W. E. Rainey 1
  • 1Department of Physiology, Medical College of Georgia, Augusta, GA, USA
  • 2Department of Pathology, Tohoku University School of Medicine, Sendai, Japan
  • 3Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA
Further Information

Publication History

received 14.04.2008

accepted 12.06.2008

Publication Date:
25 September 2008 (online)

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Abstract

Spironolactone and eplerenone are widely used as mineralocorticoid antagonists. Spironolactone has several nonspecific actions including inhibition of androgen receptor and steroid hormone biosynthesis. While studies have shown that eplerenone does not exhibit nonspecific actions on androgen receptor, its effects on steroid hormone production have not been reported. Herein, the effects of eplerenone (0.1–30 μM) and spironolactone (0.1–30 μM) on steroid production were examined in human adrenocortical H295R cells. Spironolactone inhibited basal production of cortisol (91%) and aldosterone (53%). Treatment of H295R cells with angiotensin II (Ang II) for 24 h increased aldosterone production by 11-fold. Spironolactone inhibited Ang II stimulation of aldosterone production by 80%. Addition of pregnenolone increased aldosterone (9-fold) and cortisol (3-fold) production. Spironolactone inhibited pregnenolone metabolism to aldosterone (67%) and cortisol (74%). The inhibitory effects of spironolactone occurred at concentrations far higher than those needed to block mineralocorticoid receptor, suggesting an action directly on the enzymes involved in steroid production. In contrast, eplerenone did not inhibit basal, Ang II, forskolin, pregnenolone-stimulated cortisol, or aldosterone production. Together, these data demonstrate that opposed to spironolactone, pharmacologic concentrations of eplerenone do not inhibit adrenal cell aldosterone or cortisol production.

Key words

aldosterone - cortisol - angiotensin - mineralocorticoid receptor blocker - steroid

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