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Behavioral Effects of rapid Changes in Aromatase Activity in the Central Nervous System

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Balthazart, J., Baillien, M., Cornil, C., Charlier, T., Evrard, H., & Ball, G. (2005). Behavioral Effects of rapid Changes in Aromatase Activity in the Central Nervous System. In C. Kordon, R.-C. Gaillard, & Y. Christen (Eds.), Hormones and the Brain (pp. 173-199). Berlin, Germany: Springer.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0013-D6EF-B
In many vertebrate species, male sexual behavior is activated by the action in the preoptic area of estrogens produced by the local aromatization of testosterone. Estrogens bind to intracellular receptors, which then act as transcription factors to activate the behavior. In parallel, changes in aromatase activity (AA) result from steroid-induced modifications of enzyme transcription. The transcription of aromatase is regulated in a synergistic manner by estrogenic and androgenic metabolites of testosterone. Regulatory proteins such as the steroid receptor coactivator-1 modulate steroid action in the brain, and an increasing amount of data now indicate that this mode of control is also implicated in the activation by steroids of sexual behavior and of aromatase transcription. More recently, rapid non-genomic effects of estrogens have been described in a variety of animal models, and evidence has accumulated in Japanese quail indicating that AA in the preoptic area is modulated by rapid (minute to hour) non-genomic mechanisms in addition to the slower (hours to days) transcriptional changes. Conditions that enhance protein phosphorylation, such as the presence of high concentrations of calcium, magnesium and ATP, rapidly (within min) downregulate AA in hypothalamic homogenates. Similarly, the pharmacological mobilization of intracellular calcium with thapsigargin or stimulation of various glutamate receptors (AMPA, kainate, NMDA) that lead to increased intracellular calcium concentrations depresses within minutes the AA that is measured in quail preoptic explants. Protein kinase inhibitors interfere with the calcium-induced inhibition of AA, and multiple phosphorylation consensus sites are present on the deduced amino acid sequence of quail aromatase. Fast changes in the local availability of estrogens in the brain can thus be caused by aromatase phosphorylations that rapidly regulate neuronal physiology and behavior. Recent studies suggest that the pharmacological blockade of AA by specific inhibitors rapidly down regulates motivational and consummatory aspects of male sexual behavior in quail and decreases responsiveness to painful stimuli within minutes. The rapid and slower changes of AA in the central nervous system thus match well with the genomic and non-genomic actions of estrogens and potentially provide temporal variations in the bioavailability of estrogens that can support the entire range of established effects for this steroid.