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

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Summary

Introduction

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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