7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases.
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.
Auci
Dominick L
DL
HollisEden Pharmaceuticals, San Diego, CA 92121, USA. Dauci@holliseden.com
Reading
Christopher L
CL
Frincke
James M
JM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology
C524733:17-ethynyl-5-androstene-3, 7, 17-triol; D000893:Anti-Inflammatory Agents; D003687:Dehydroepiandrosterone