Washington, April 1 : Researchers at the University of Alabama at Birmingham have identified the receptor pathway that estrogen uses to decrease liver injury after trauma and hemorrhage.

“G protein-coupled receptor 30-dependent protein kinase A pathway is critical in nongenomic effects of estrogen in attenuating liver injury after trauma-hemorrhage,” say the study authors.

Estrogen directs cellular processes in two ways-by interacting with DNA to produce new protein or by binding cell surface receptors to initiate rapid protein signaling. The available data shows that cell surface receptors may be helpful in improving recovery from liver injury following soft-tissue trauma and major blood loss, but which receptor is responsible for this effect was not known until this study was performed.

Led by Irshad H. Chaudry of the university, the researchers conducted a study to answer this question using a rat model of liver injury and hemorrhage. They examined the cell surface receptor pathways by treating rats with a form of estrogen that cannot enter cells, thus acting only via cell surface interactions.

It was found that rats affected by trauma-hemorrhage released high levels of liver enzymes associated with liver damage, but the treatment with surface estrogen decreased the amount of enzymes released.

The treatment also maintained normal levels of cell-protective Bcl-2 and active protein kinase A, which were otherwise decreased by trauma-hemorrhage.

Thereafter, the researchers examined two possible receptors-G protein-coupled receptor 30 (GPR30) and estrogen receptor-alpha-for their role in mediating estrogen’s protective effects.

They noted that receptor expression on the cell surface was diminished by blocking protein production in cultured liver cells. Blockade of estrogen receptor-alpha had no effect on cells, but GPR30 silencing resulted in decreased Bcl-2 and active protein kinase A.

The identification of GPR30 and the downstream pathways involved in estrogen’s beneficial effects provide new insights in resolving liver injury following tissue trauma and major blood loss, for specific activation of these protein pathways may provide novel therapeutics for treating trauma patients.

The study has been published in The American Journal of Pathology. (ANI)