The scientists found evidence that the progesterone metabolite allopregnanolone reduces the brain's response to corticotropin-releasing factor (CRF), a peptide hormone that plays an important role in the stress response in animals. The finding, which was reported in the Nov. 10, 2004 edition of the Journal of Neuroscience, could provide a new drug target for treating anxiety and depression in women.
In the study, Emory researchers Donna Toufexis, PhD, Michael Davis, PhD and Carrie Davis, BS, and Alexis Hammond, BS, of Spelman College, compared how female rats with different levels of the sex hormones, estrogen and progesterone, reacted to loud noises after injections of CRF into the brain's lateral ventricles. CRF injections usually increase the "acoustic startle response" in this test used to gauge stress and anxiety, a phenomenon called CRF-enhanced startle.
In the first experiment, the scientists compared acoustic startle responses after CRF injection in an estrogen-only group, an estrogen-plus-progesterone group and a control group that did not receive any sex hormones. All the rats lacked ovaries and the ability to produce sex hormones naturally. Acoustic startle response was unaffected in the estrogen-only group and the control group. In the estrogen-plus-progesterone group, however, CRF-enhanced startle was significantly lower than in the other groups.
In another set of experiments, the researchers discovered that lactating female rats with naturally high levels of progesterone had markedly lower CRF-enhanced startle responses compared to virgin females with intact ovaries. "Findings from theses initial experiments pointed toward the conclusion that progesterone inhibits the effect of CRF on the acoustic startle response," said Toufexis.