Brain Research, 125 (1977) 313-324 313 © Elsevier/North-Holland Biomedical Press, Amsterdam - Printed in The Netherlands PROGESTERONE METABOLISM IN THE PINEAL, BRAIN STEM, THALA- MUS AND CORPUS CALLOSUM OF THE FEMALE RAT ISRAEL HANUKOGLU, HARRY J. KARAVOLAS* and ROBERT W. GOY Department of Physiological Chemistry, The Waisman Centerfor Mental Retardation, and The Regional Primate Research Center, University of Wisconsin, Madison, Wisc. 53706 (U.S.A.) (Accepted August 13th, 1976) SUMMARY Specific brain regions, namely, thalamus, tectum, tegmentum, cerebellum, medulla and pineal, from five proestrous rats were incubated for 30 min with Jail]- progesterone. After reverse isotopic dilution analysis, the following metabolites were identified in all incubations by purification to constant specific activity, deriva- tive formation and/or gas liquid chromatography trapping: [aH]5a-pregnane-3, 20- dione (10-20~ of the starting substrate except pineal -- 0.7~), [ZH]3a-hydroxy- 5a-pregnan-20-one (1.6-3.8~o except for pineal -- 0.5~) and [aH]20a-hydroxy-4- pregnen-3-one (0.05-0.11 ~). Preliminary results from the corpus collosum incuba- tion indicated the presence of the same metabolites. Although some apparent constant specific activities were obtained for 20a-hydroxy-5a-pregnan-3-one and 5fl-pregnane- 3, 20-dione, the low levels of aH associated with these steroids did not permit a defin- itive identification. The results indicate the presence of at least A4-steroid 5a-reduc- tase, 3a-hydroxysteroid dehydrogenase and 20a-hydroxysteroid dehydrogenase activ- ities with progesterone as substrate in the brain regions examined. INTRODUCTION The hypothalamus and anterior pituitary are well established loci of action for some neuroendocrine effects of progesterone 1,**. Recently other discrete regions of the central nervous system, e.g., thalamus, mesencephalon, cerebellum, medulla * Please address reprint requests to Dr. H. J. Karavolas, 707A Waisman Center, 2605 Marsh Lane, Madison, Wisc. 53706, U.S.A. ** Trivial steroid names and abbreviations used are: progesterone, 4-pregnene-3, 20-dione; 5a-dihydro- progesterone (5a-DHP), 5a-pregnane-3, 20-dione; 5fl-dihydroprogesterone (5fl-DHP), 5/~-pregnane- 3, 20-dione; testosterone, 17fl-hydroxy-4-androsten-3-one.