Figure 4.

Novel pathways and oxygenation products from DHEA. DHEA is first converted to 17-HpDHEA by 15-LOX. Next, 17-HpDHEA is partially reduced to the oxide radical, which reacts with the vicinal double bond at the 16-position to yield the 16(17)-epoxide radical (see text and Yang et al., 2011). Non- or low stereospecific addition of oxygen to the intermediate leads to formation of two types of peroxide radical diastereomers; their further reduction produces 13-HEDPEA and 15-HEDPEA. Via a LOX-related mechanism, 17-HpDHEA is converted to 10, 17S-diHDHEA or directly reduced to 17S-HDHEA. 10, 17S-diHDHEA, and 15-HEDPEA block PMN chemotaxis, reduce P-selectin expression and aggregation of platelets and leukocytes, and show organ protection in ischemia/reperfusion injury. Although these new products directly act on recombinant CB2 receptors in vitro, the activation of CB2 in vivo and/or additional receptors in vivo by 10,17S-diHDHEA and 15-HEDPEA remains of interest.