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The Role of Androgen Metabolism in the Activation of Male Behavior a

Although we have begun to realize the importance of hormone metabolism in modulating an individual's response to particular gonadal hormones, the full import of normal metabolic influences still escapes us. For many years, scientists interested in endocrine function in the male focused primarily on the production of testosterone (T). T metabolism was viewed primarily as a catabolic process, resulting in the breakdown of the active hormone and its excretion. A large number of androgenic metabolites were identified, but most of them were ignored because they had minimal biological potency when their activity was assessed in various bioassay systems such as rat seminal vesicle or chick comb. One exception to this was 5a-dihydrotestosterone (DHT). First, DHT was shown to be more potent than testosterone in several bioassay systems, and then in the sixties, conclusive evidence was published which documented the local formation of DHT in male sexual accessory tissues. These findings sparked research on the importance of local metabolism in increasing, as well as decreasing, the biological activity of gonadal hormones. Research on the formation and mechanism of action of DHT in the sexual accessory tissues proved invaluable in developing a general model of androgen metabolism and action. The higher concentrations and more uniform distribution of hormones and hormone receptors in peripheral tissues allowed researchers to carry out studies on these tissues which were not technically or practically feasible in brain tissue. Ironically, the focus on sexual accessory tissues led many to ignore metabolic pathways other than Sa-reduction, but when scientists began to study the role of androgen metabolism in the activation of behavior, it became obvious that other metabolic pathways were also important, since DHT showed limited effectiveness in activating normal levels of male social behavior. This pointed to the importance of another metabolic process, the aromatization of androgens to estrogens, for estrogenic metabolites play an important role in activating male behaviors in many species. This research has highlighted the possibility that many behaviors which have been described as androgen dependent will prove in fact to be dependent on estrogens formed from androgenic precursors. Aromatization and 5a-reduction are opposing metabolic pathways. That is, once an androgen is Sa-reduced, most evidence suggests that it can no longer be converted