Estrogen reduces the neurite growth of serotonergic cells expressing estrogen receptors

Serotonergic innervation of the central nervous system has a sexual dimorphism. The serotonin level in the hypothalamus was modulated by estrogen, and the formation of sexual dimorphism of serotonergic fiber innervation in the hypothalamus has been shown by the effect of sexual hormone during the critical perinatal period. In this study, we examined the direct effect of estrogen on the neurite growth of serotonergic neurons in primary culture from embryonic day 14 (E14) of rat mesencephalon. The total neurite length of serotonin-immunoreactive (IR) cells was significantly decreased by estradiol benzoate (E2, 10(-8)M) treatment for 7 days, compared with the case of no treatment. Moreover, the presence of estrogen receptor (ER) alpha and ERbeta mRNA in the E14 mesencephalon with reverse transcription-polymerase chain reaction (RT-PCR), and the ERalpha or ERbeta protein in the cultured serotonin-IR cells with double fluorescence immunohistochemistry were also demonstrated. Our results suggest that the inhibitory effects of E2 on the neurite growth of serotonergic cells expressing ERalpha or ERbeta might be involved in the formation of the sexual dimorphic distribution of serotonergic innervation.