BRAIN AROMATASE AND THE CONTROL OF MALE SEXUAL-BEHAVIOR

The activational effects of testosterone (T) on male copulatory behavi or are mediated by its aromatization into estradiol. In quail, we have shown by stereotaxic implantation of steroids and metabolism inhibito rs and by electrolytic lesions that the action of T and its aromatizat ion take place in the sexually dimorphic medial preoptic nucleus (POM) . The distribution and regulation of brain aromatase was studied in th is species by product-formation assays measuring aromatase activity (A A) in microdissected brain regions and by immunocytochemistry (ICC). A romatase-immunoreactive (ARO-ir) neurons were found in four brain regi ons: the POM, the septal region, the bed nucleus of the stria terminal s (BNST) and the tuberal hypothalamus. ARO-ir cells actually outline t he POM boundaries. ARO-ir material is found not only in the perikarya of neurons but also in the full extension of their cellular processes including the axons and the presynaptic boutons. This is confirmed at the light level by the demonstration of immunoreactive fibers and punc tate structures in brain regions that are sometimes fairly distant fro m the closest ARO-ir cells. A lot of ARO-ir cells in the POM and BNST do not contain immunoreactive estrogen receptors (ER-ir) as demonstrat ed by double label ICC. These morphological data suggest an unorthodox role for the enzyme or the locally formed estrogens. In parallel with copulatory behavior, the preoptic AA decreases after castration and i s restored by T to levels seen in sexually mature males. This probably reflects a change in enzyme concentration rather than a modulation of the activity in a constant number of molecules since the maximum enzy matic velocity (V(max)) only is affected while the affinity (K(m)) rem ains unchanged. In addition, T increases the number of ARO-ir neurons in POM and other brain areas suggesting that the concentration of the antigen is actually increased. This probably involves the direct activ ation of aromatase transcription as demonstrated by RT-PCR studies sho wing that aromatase mRNA is increased following T treatment of castrat es. These activating effects of T seem to result from a synergistic ac tion of androgenic and estrogenic metabolites of the steroid. The anat omical substrate for these regulations remains unclear at present espe cially in POM where ARO-ir cells do not in general contain ER-ir while androgen receptors appear to be rare based on both [H-3] dihydrotesto sterone autoradiography and ICC. Transynaptic mechanisms of control ma y be considered. A modulation of brain aromatase by catecholamines is also suggested by a few pharmacological studies. This notion is furthe r supported by anatomical data demonstrating dense projections of dopa mine beta-hydroxylase and tyrosine hydroxylase-immunoreactive fibers a round ARO-ir cells.