Journal
HORMONE AND METABOLIC RESEARCH
Volume 41, Issue 1, Pages 35-39Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0028-1087188
Keywords
aldosterone; cortisol; angiotensin; mineralocorticoid receptor blocker; steroid
Categories
Funding
- National Institutes of Health [DK43140]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK043140, R29DK043140] Funding Source: NIH RePORTER
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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 mu M) and spironolactone (0.1-30 mu M) 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 If (Ang II) for 24h 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.
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