'Master' Stress Hormone Prevents Mother From Rejecting Embryo.

2001 OCT 25 - (NewsRx.com & NewsRx.net) -- The "master" hormone that commands the body's response to stress is also directly involved in the process that prevents a mother's immune system from destroying an embryo that has implanted in her uterus, according to the results of a study by researchers at the National Institute of Child Health and Human Development, The National Institute of Diabetes and Digestive and Kidney Diseases, and several other Institutions.

"This finding opens up promising new ground in the quest to treat recurrent miscarriage, " explained Duane Alexander, MD, director of the NICHD. "Similarly, the finding may also lead to new insights for preventing and treating preeclampsia, a life-threatening complication of pregnancy, as well as certain forms of cancer."

The study appears in the October 9, 2001 issue of Nature Immunology. The researchers have found that the stress hormone corticotropin releasing hormone (CRH) is also produced by trophoblasts - early cells that later give rise to the placenta, explained the study's senior author, George P. Chrousos, MD, chief of NICHD's Pediatric and Reproductive Endocrinology Branch. In turn, CRH causes these same cells to secrete a protein known as Fas ligand - FasL, for short.

Like a key fits into a lock, FasL fits into the Fas molecule that sits on the surface of immune cells known as T-cells. Once FasL binds to the Fas molecule, the T-cell enters into a stage known as apoptosis, a programmed cycle that brings on its own death. The entire process destroys the T cells before they can attack the developing embryo. The Fas molecule is technically known as a receptor. The "lock and key" mechanism of a molecule and its receptor occurs with a vast number of cell and hormone combinations, triggering a variety of courses of action for the cell.

In an earlier study, these researchers found that the cells lining the uterus also produce CRH. In this study, the researchers found that the cells lining the uterus also manufacture FasL.

"The embryo is foreign to its mother, and, in theory, should be rejected by her immune system," Chrousos said. "When the embryo first implants, the surrounding tissue even looks inflamed, as if it were responding to an infection."

Chrousos and his colleagues reached their conclusions after performing an elaborate series of experiments on cells in culture and in animals. First, the researchers tested both laboratory cultures of human trophoblast cells and human cancer cells that resemble trophoblast cells. Both types of cells were found to produce large amounts of CRH. Also, both cell types had receptors for CRH on their cell surfaces, which suggests that the cells react to the CRH that they themselves produce.