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

Steroids. 2011 Jan;76(1-2):145-55. doi: 10.1016/j.steroids.2010.10.005. Epub 2010 Oct 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Androstenols / chemistry
  • Androstenols / metabolism
  • Androstenols / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred Strains
  • Middle Aged
  • Molecular Conformation
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Prostatitis / drug therapy*
  • Prostatitis / metabolism
  • Rats
  • Solubility
  • Stereoisomerism
  • Young Adult

Substances

  • Androstenols
  • Anti-Inflammatory Agents
  • androst-5-ene-3,7,16,17-tetrol