Estradiol-17β increase serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain

The aim of the present study was to determine the effect of estradiol-17β (E2), in its positive feedback mode for gonadotropin release, on the serotonin transporter (SERT) in female rat brain. Levels of SERT mRNA were determined by in situ hybridization and SERT-binding sites were measured by quantitative [3H]paroxetine receptor autoradiography. The injection of estradiol benzoate (EB) in acutely ovariectomized rats increased significantly (∼ 50%) the numbers of cells that expressed SERT mRNA in the dorsal raphe nucleus and the density of SERT-binding sites in lateral septum (90%), basolateral amygdala (20%), ventral nucleus of thalamus (250%) and ventromedial hypothalamic nucleus (250%). SERT-binding sites in EB-treated rats were significantly lower in periaqueductal central grey (15%). These findings indicate that effects on SERT gene expression may be involved in the E2-induction of the gonadotropin surge. Together with our previous findings, they also suggest that the sex differences in depression and the apparent psychotropic effect of E2 may be due to the action of E2 on the serotonin transporter as well as 5-HT2A receptors.