Rapid and reversible inhibition of brain aromatase activity

Many actions of androgens require their conversion via the enzyme aromatase into oestrogens. Changes in brain aromatase activity are thought to take p lace via changes in enzyme concentration mediated by effects of sex steroid s on aromatase transcription. These changes are relatively slow which fits in well with the fact that oestrogens are generally viewed as slow-acting m essengers that act via changes in gene transcription. More recently, fast a ctions of oestrogens, presumably at the level of the cell membrane, have be en described both in the female brain and in the male brain after the conve rsion of testosterone to oestradiol. It is difficult to reconcile the slow regulation of oestrogen synthesis (that occurs via changes in aromatase con centration) with a rapid action at the membrane level. Even if fast transdu ction mechanisms are available, this will not result in rapid changes in br ain function if the availability of the ligand does not also change rapidly . Here, we report that aromatase activity in neural tissue of male Japanese quail (Coturnix japonica) is rapidly downregulated in the presence of Mg2, Ca2+ and ATP in hypothalamic homogenates and in brain explants exposed to high Ca2+ levels following a K+-induced depolarization or the stimulation of glutamate receptors. The K+-induced inhibition of aromatase activity is observed within minutes and reversible. Given that aromatase is present in presynaptic boutons, it is possible that rapidly changing levels of locally produced oestrogen are available for nongenomic regulation of neuronal phy siology in a manner more akin to the action of a neuropeptide than previous ly hypothesized.