REGIONAL AND INTERSPECIES DIFFERENCES IN BRAIN PROGESTERONE METABOLISM

Metabolites of [H-3]progesterone were studied in slices prepared from different brain regions of male rat, mouse, and monkey. The major metabolites were 5alpha-dihydroprogesterone (5alpha-DHP) and 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) in rat brain slices, 5alpha-DHP and 20alpha-dihydroprogesterone (20alpha-DHP) in mouse brain slices, and 20alpha-DHP in monkey brain slices. In rat olfactory bulb slices, 5alpha-DHP represented 25.2 +/- 3.3% of total radioactivity and 3alpha,5alpha-THP 17.5 +/- 2.8%, whereas in rat medulla oblongata slices, 5alpha-DHP was 31.3 +/- 3.5% and 3alpha,5alpha-THP 5.4 +/- 1.5% of total radioactivity. In slices from other rat brain regions, both metabolites represented 12-20% of total radioactivity. The highest metabolite content in mouse brain was also detected in olfactory bulb slices, where 5alpha-DHP represented 16.6 +/- 4.6% and 20alpha-DHP 9.5 +/- 2.3% of total radioactivity. In cortical and corpus callosum slices of monkey brain, 26.8 +/- 4.4% and 2.4 +/- 0.5% of total radioactivity, respectively, were converted to 20alpha-DHP, and less than 3% of total radioactivity could be attributed to any of the other metabolites detected. The 3alpha,5alpha-THP content in both rat and monkey brain was below 1 nM, but increased in rat brain to 6.7 +/- 2.5 nM after electroshock. Endogenous 3alpha,5alpha-THP might play an important role in the regulation of rat behavior through the modulation of GABA action on the GABA(A) receptor. The significant interspecies differences in the brain progesterone metabolism should be considered in evaluating the functional role of neurosteroids in various species.