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Rapid Control of Brain Aromatase Activity by Glutamatergic Inputs

University of Liege, Center for Cellular and Molecular Neurobiology, Research Group in Behavioral Neuroendocrinology (J.B., M.B.), B-4000 Liege 1, Belgium; and Department of Psychological and Brain Sciences, Johns Hopkins University (G.F.B.), Baltimore, Maryland 21218

Address all correspondence and requests for reprints to: Dr. Jacques Balthazart, Center for Cellular and Molecular Neurobiology, Research Group in Behavioral Neuroendocrinology, University of Liege, 1 boulevard de l’Hopital (Bâtiment B36), B-4000 Liege 1, Belgium. E-mail: jbalthazart{at}ulg.ac.be.

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca²⁺ concentrations, such as the addition of glutamate agonists (kainate, -amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-D-aspartate), but not of -aminobutyric acid. The kainate effects, which reduce aromatase activity by 25–50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators.

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