Effect of vorozole, an aromatase enzyme inhibitor, on sexual behavior, aromatase activity and neural immunoreactivity.

Aromatase enzyme is essential for the expression of normal sexual behavior in many mammals and birds. Here we report that vorozole (R83842), a non-steroidal aromatase inhibitor, blocks sexual behavior in the female musk shrew. In addition, vorozole treatment lowers aromatase activity in male and female preoptic area, and reduces plasma estradiol concentrations in females. Our findings confirm and extend results demonstrated in other species, conducted with the active enantiomer (R83842), or the racemic mixture (R76713, racemic vorozole). We also report that vorozole treatment affects the immunocytochemical distribution of aromatase immunoreactivity (AROM-ir) in musk shrew brain. The histological identification of neurons that contain this enzyme has been difficult in mammals. Several aromatase enzyme antisera have been developed and used in brain, and each gives a different pattern of immunoreactivity. Moreover, despite the fact that aromatase activity is very high in the bed nucleus of the stria terminalis, several amygdala nuclei, the preoptic area and hypothalamus, AROM-ir in these regions has been very limited. The distribution of AROM-ir in female musk shew brain tissues is modified by treatment with vorozole prior to sacrifice. Female musk shrew brains contain aromatase immunoreactive cell bodies, as reported previously, in the central amygdala, lateral septum and to a limited extent in the bed nucleus of the stria terminalis (BST). Brains of females treated with vorozole show additional immunoreactivity in the preoptic area, hypothalamus, and medial amygdala, and have a broad distribution of AROM-ir in several subdivisions of the BST. Several sexual dimorphisms are apparent in musk shrews brains after treatment with vorozole. We have quantified this sexual dimorphism in the medial preoptic area (MPO) by counting immunoreactive cells. In both the rostral and caudal portions of the MPO, female brains contain significantly fewer AROM-ir cell bodies than males. These data are in complete agreement with sex differences in biochemical analyses of aromatase activity in the MPO. At this time we do not know if these dimorphisms are the result of differences in circulating levels of steroids in males and females, and/or if the AROM-ir nuclei regulate sexually dimorphic behaviors.