It was known that estrogen, a female sex hormone, increases host response after traumatic injury on the liver after trauma and hemorrhage; but the precise cellular pathway was not known.

Estrogen heads cellular activities in two ways: by activating some DNA patches to synthesize new protein or by attaching to cell surface receptors to start rapid protein signaling.

Current knowledge points to cell surface receptors in increasing recovery from liver injury after soft-tissue trauma and major blood loss, but nobody knew precisely which receptor was responsible for all these effects.

The research team headed by Irshad H. Chaudry at the University of Alabama at Birmingham looked for an answer through investigations on an established rat model of liver injury and hemorrhage.

The researchers analyzed the cell surface receptor pathways by treating rats with a type of estrogen that cannot enter cells, thus the hormone was active just on the cell surface. As expected, rats affected by trauma-hemorrhage released high levels of liver enzymes associated with liver damage. But the treatment with surface estrogen dropped the levels of synthesized enzymes.

The estrogen also kept normal levels of cell-protective Bcl-2 and active protein kinase A, which were otherwise diminished by trauma-hemorrhage. The team then focused on two possible receptors, G protein-coupled receptor 30 (GPR30) and estrogen receptor-alpha, for their importance on inducing the estrogen's protective effects.

In cultured liver cells, researchers could decrease the synthesis of the receptors on the cell surface. Blocking the protein synthesis of estrogen receptor-alpha did not induce any effect on the cells, but GPR30 removal produced a drop on Bcl-2 and active protein kinase A. Thus GPR30 and the downstream pathways (Bcl-2 and active protein kinase A) are connected to the estrogen's beneficial effects. Specific turn on of these protein pathways could deliver new therapeutics for treating trauma patients.