Inhibition of aggression by progesterone and its metabolites in female Syrian hamsters

The sequence of estradiol and progesterone is known to inhibit the expressi on of aggression in female hamsters. Despite the key importance of progeste rone in the inhibition of aggression, little is known of the mechanisms thr ough which progesterone may exert this effect. Three experiments were perfo rmed to assess the degree to which metabolites of progesterone can affect a ggression in female Syrian hamsters. Systemic estradiol treatment followed by injections of either progesterone (300 mug IP) or 4-pregnen-21-ol-3,20-d ione (DOC, 300 etag IP) reliably inhibited aggression. Systemic injection ( 75, 150, or 300 mug IP) of either 5 alpha -pregnan-3 alpha ,21-diol-20-one (THDOC) or 5 alpha -pregnan-3 alpha -ol-20-one (3 alpha ,5 alpha -THP) did not affect aggression. Intracerebroventricular infusion of 3 alpha ,5 alpha -THP following systemic estradiol treatment also did not affect aggression . In a third experiment, female hamsters were given systemic treatments wit h estradiol and progesterone that were subthreshold with respect to inhibit ion of aggression. In these females, intracerebroventricular infusion of TH DOC inhibited aggression. These results indicate that metabolites of proges terone can inhibit aggression, most notably in synergy with progesterone it self. (C) 2001 Wiley-Liss, Inc.