Regional and interspecies differences in brain progesterone metabolism

Metabolites of [3H]progesterone were studied in slices prepared from different brain regions of male rat, mouse, and monkey. The major metabolites were 5 alpha-dihydroprogesterone (5 alpha-DHP) and 3 alpha,5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP) in rat brain slices, 5 alpha-DHP and 20 alpha-dihydroprogesterone (20 alpha-DHP) in mouse brain slices, and 20 alpha-DHP in monkey brain slices. In rat olfactory bulb slices, 5 alpha-DHP represented 25.2 +/- 3.3% of total radioactivity and 3 alpha,5 alpha-THP 17.5 +/- 2.8%, whereas in rat medulla oblongata slices, 5 alpha-DHP was 31.3 +/- 3.5% and 3 alpha,5 alpha-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 5 alpha-DHP represented 16.6 +/- 4.6% and 20 alpha-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 20 alpha-DHP, and less than 3% of total radioactivity could be attributed to any of the other metabolites detected. The 3 alpha, 5 alpha-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 3 alpha,5 alpha-THP might play an important role in the regulation of rat behavior through the modulation of GABA action on the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)