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7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Dominick L. Auci, a, , Christopher L. Readinga and James M. Frinckea
aHollisEden Pharmaceuticals, 4435 Eastgate Mall, Suite 400, San Diego, CA 92121, United States
Received 2 November 2008; accepted 20 November 2008. Available online 9 December 2008.
Abstract
The metabolome of dehydroepiandrosterone (DHEA), the most abundant adrenal steroid in the human body, includes androgens, estrogens and a series of immune regulating hormones that lack androgenic or estrogenic activity. Of these, 7-hydroxy derivatives, once considered physiologically inactive end products of metabolism, possess a combination of potent anti-inflammatory and immune modulating activity without androgenic or estrogenic capacity. Oxygenated metabolites derived from androstenediol (AED), the predominant precursor in rodents, may be responsible for many activities initially attributed to exogenous DHEA administered to rodents. We here review the discovery of these compounds in models of inflammation and autoimmune diseases, discuss the potential mode of action and trace the development of a specific synthetic derivative, which is less labile to metabolism and which may at last deliver to humans the benefits of DHEA observed in rodents.
http://www.sciencedirect.com/science...380342e2446bea
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Dominick L. Auci, a, , Christopher L. Readinga and James M. Frinckea
aHollisEden Pharmaceuticals, 4435 Eastgate Mall, Suite 400, San Diego, CA 92121, United States
Received 2 November 2008; accepted 20 November 2008. Available online 9 December 2008.
Abstract
The metabolome of dehydroepiandrosterone (DHEA), the most abundant adrenal steroid in the human body, includes androgens, estrogens and a series of immune regulating hormones that lack androgenic or estrogenic activity. Of these, 7-hydroxy derivatives, once considered physiologically inactive end products of metabolism, possess a combination of potent anti-inflammatory and immune modulating activity without androgenic or estrogenic capacity. Oxygenated metabolites derived from androstenediol (AED), the predominant precursor in rodents, may be responsible for many activities initially attributed to exogenous DHEA administered to rodents. We here review the discovery of these compounds in models of inflammation and autoimmune diseases, discuss the potential mode of action and trace the development of a specific synthetic derivative, which is less labile to metabolism and which may at last deliver to humans the benefits of DHEA observed in rodents.
http://www.sciencedirect.com/science...380342e2446bea
