Abstract
Specific brain regions, namely, thalamus, tectum, tegmentum, cerebellum, medulla and pineal, from five proestrous rats were incubated for 30 min with [ 3H]progesterone. After reverse isotopic dilution analysis, the following metabolites were identified in all incubations by purification to constant specific activity, derivative formation and/or gas liquid chromatography trapping: [ 3H]5α-pregnane-3, 20-dione (10–20% of the starting substrate except pineal — 0.7%), [ 3H]3α-hydroxy-5α-pregnan-20-one (1.6–3.8% except for pineal — 0.5%) and [ 3H]20α-hydroxy-4-pregnen-3-one (0.05–0.11%). Preliminary results from the corpus collosum incubation indicated the presence of the same metabolites. Although some apparent constant specific activities were obtained for 20α-hydroxy-5α-pregnan-3-one and 5β-pregnane-3, 20-dione, the low levels of 3H associated with these steroids did not permit a definitive identification. The results indicate the presence of at least Δ 4-steroid 5α-reductase, 3α-hydroxysteroid dehydrogenase and 20α-hydroxysteroid dehydrogenase activities with progesterone as substrate in the brain regions examined.
Highlights
The hypothalamus and anterior pituitary are well established loci of action for some neuroendocrine effects of progesterone 1,**
Pineal, have been suggested as target sites for progesterone on the basis of several methodological approaches: (a) observations of central nervous system (CNS) related variables (lordosis, luteinizing hormone-releasing factor (LHRF) stores) in the presence of progesterone implants in the brain25,3°; (b) observations of variables within specific regions of the CNS, following progesterone treatment either in vitro or in vivog,13,2°; (c) correlations of variables (MAO, HIOMT) from specific regions of the CNS with different reproductive stages of females that are modulated by progesterone[12,44]; and (d) analyses of regional radioactivity uptake after [3H]progesterone treatmentgA4,22, 38
Previous in vitro studies have shown that rat hypothalamus and anterior pituitary can metabolize progesterone to 5a-dihydroprogesterone (5a-DHP), 3a-hydroxy-5a-pregnan-20-one and to trace amounts of 20a-hydroxy-4-pregnen-3-one
Summary
The hypothalamus and anterior pituitary are well established loci of action for some neuroendocrine effects of progesterone 1,**. Previous in vitro studies have shown that rat hypothalamus and anterior pituitary can metabolize progesterone to 5a-dihydroprogesterone (5a-DHP), 3a-hydroxy-5a-pregnan-20-one and to trace amounts of 20a-hydroxy-4-pregnen-3-one In recent in vivo uptake studies, accumulation of [3H]5a-DHP in these neuroendocrine centers and cerebral cortex was demonstrated with either [3H]progesterone or [3H]5a-DHP 14. 5a-DHP was shown to have some progesterone-like effects on neuroendocrine processes such as gonadotropin regulation 15 and lordosis behavior4,23, 4°. These observations support a hypothesis that metabolism of progesterone in these neural centers may be a requisite step for some or all of its actions
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