We recently showed that the expression of progesterone receptor (PR) mRNA in the neocortex and hippocampus was significantly affected by estrogen in adult ovariectomized rats. To gain a better understanding of sex differences in brain functions, we examined whether the expression of PR mRNA in these areas of male rats was affected by estrogen or not. Adult orchiectomiaed (ORX) rats were given a subcutaneous injection of 200 μl of sesame oil containing 10 μg or 100 μg of 17β-estradiol and were killed 6, 12, and 24 h after the injection. Some rats were also killed after injection of sesame oil alone as control. At each time point, the frontal cortex, occipital cortex, temporal cortex, and hippocampus were collected, and the expression of PR mRNA in each brain area was measured by Northern blot. The results showed that estrogen had only minor effects on the expression of PR mRNA in the neocortex and the hippocampus of ORX rats; 100 μg of 17β-estradiol slightly but significantly increased the expression of PR mRNA in the frontal cortex and hippocampus, but had no significant effect in the occipital cortex and temporal cortex. Ten μg of 17β-estradiol had no significant effect on the expression of PR mRNA in areas we examined. Together with results in ovariectomized rats that either 10 μg or 100 μg of 17β-estradiol increased the expression of PR mRNA in the frontal cortex and hippocampus, we suggest that estrogen stimulates the frontal cortex and hippocampus by increasing the expression of PR mRNA only in female rats but not in male rats. [Jpn J Physiol 55 Suppl:S213 (2005)]