Steroid metabolism in the brain: From bird watching to molecular biology, a personal journey

Since Arnold Adolph Berthold established in 1849 the critical role of the testes in the activation of male sexual behavior, intensive research has identified many sophisticated neurochemical and molecular mechanisms mediating this action. Studies in Japanese quail demonstrated the critical role of testosterone action and of testosterone aromatization in the sexually dimorphic medial preoptic nucleus in the activation of male copulatory behavior. The development of an immunohistochemical visualization of brain aromatase in quail then allowed further refinement in the localization of the sites of neuroestrogens production. Testosterone aromatization is required for the activation of both appetitive and consummatory aspects of male sexual behavior. Brain aromatase activity is modulated by steroid-induced changes in the transcription of the corresponding gene but also more rapidly by phosphorylation processes. Sexual interactions with a female also rapidly regulate brain aromatase activity in an anatomically specific manner presumably via the release and action of endogenous glutamate. These rapid changes in estrogen production modulate sexual behavior and in particular its motivational component with latencies ranging between 15 and 30min. Brain estrogens seem to act in a manner akin to a neurotransmitter or at least a neuromodulator. More recently, assays of brain estradiol concentrations in micropunched samples or in dialysis samples obtained from behaviorally active males suggested that aromatase activity measured ex vivo might not be an accurate proxy to the rapid changes in local neuroestrogens production and concentrations. Studies of brain testosterone metabolism are thus not over and will keep scientists busy for a little longer. Elsevier SBN Keynote Address, Montreal.