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Eur J Pharmacol. 2004 Dec 15;506(2):129-32.

3alpha,5beta-Reduced cortisol exhibits antagonist properties on cerebral cortical GABA(A) receptors.

Author information

1
Department of Pharmacology, Bowles Center for Alcohol Studies, CB No. 7178, 3027 Thurston Bowles Building, UNC School of Medicine, Chapel Hill, NC 27599, USA.

Abstract

The tetrahydro-reduced derivatives of progesterone and deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone are potent positive modulators of GABA(A) receptors that are elevated by hypothalamic-pituitary-adrenal axis activation in rodents. In humans, 11-deoxycortisol and cortisol are important hypothalamic-pituitary-adrenal axis steroids. We hypothesized that C(3,5) reduction of 11-deoxycortisol and cortisol generates steroids with GABA(A) receptor activity. 3alpha,5beta-Reduced cortisol dose-dependently inhibited muscimol-stimulated chloride flux and tetrahydrodeoxycorticosterone potentiation of muscimol responses. Cortisol, 11-deoxycortisol, 5alpha-dihydrocortisol, 3alpha,5alpha-reduced cortisol, 3alpha,5alpha-reduced 11-deoxycortisol, and 3alpha,5beta-reduced 11-deoxycortisol had no activity at 1 muM and weaker negative modulatory activity at 10 muM. We conclude that cortisol metabolism may produce antagonistic GABAergic activity.

PMID:
15588732
DOI:
10.1016/j.ejphar.2004.11.007
[Indexed for MEDLINE]

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