Novel components of the human metabolome: The identification, characterization and anti-inflammatory activity of two 5-androstene tetrols

Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β,16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α,17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis.

Research highlights▶ 5-Androstene tetrols are DHEA metabolites found naturally in human plasma. ▶ Tetrols are orally bioavailable and resistant to primary and secondary metabolism. ▶ Tetrols do not bind or transactivate steroid binding nuclear hormone receptors. ▶ Exogenous tetrols are very well tolerated in murine toxicity studies. ▶ Exogenous tetrols have anti-inflammatory activity in rodent models.