Expression of estrogen receptors (alpha, beta) and androgen receptor in serotonin neurons of the rat and mouse dorsal raphe nuclei; sex and species differences.

Sex steroids have been inferred to be involved in the regulation of affective status at least partly through the serotonergic (5-HT) system, particularly in the dorsal raphe nucleus (DRN), which innervates enormous projections to the cerebral cortex and limbic system. In the present study, the expression of estrogen receptors-alpha and -beta (ERalpha, ERbeta), androgen receptor (AR) and 5-HT was examined immunohistochemically in the rat and mouse DRN in both sexes. The results showed that large numbers of ERalpha- and/or ERbeta-immunoreactive (ERalpha-I, ERbeta-I) cells were found in the DRN of both male and female mice, whereas only small numbers of ERalpha-I cells and no ERbeta-I cells were seen in the rat DRN of each sex. With respect to AR-immunoreactive (AR-I) cells, moderate numbers of such cells were present only in male rats and mice, and no or very few could be observed in female ones. The ERalpha-I, ERbeta-I, and AR-I cells were mainly distributed in the rostral DRN. In double-immunostaining, many 5-HT-I neurons were found to show ERalpha and/or ERbeta expression specifically in the rostral DRN (particularly dorsal, ventral and interfascicular parts) of mice of both sexes, but not in that of rats. In contrast, only a few 5-HT neurons were observed to show AR expression in the DRN of both rodents. The current results strongly suggest that sex steroids can modulate the affective regulation of the serotonergic system through ERalpha and/or ERbeta in 5-HT neurons of the mouse rostral DRN (but not so much through AR), and that such effects might be different depending on the sex and species, as shown by the prominent sex differences in AR expression and prominent species differences in ERalpha and ERbeta expression.