Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques

It has been widely hypothesized that the ovarian steroids, estrogen (E) and progesterone (P), act on serotonin neurons to modulate mood and increase prolactin secretion in women. However, information is needed on the molecular consequences of ovarian hormone action in serotonin neurons. This study examined the effect of E and P on the expression of mRNA for the serotonin re-uptake transporter (SERT) in monkeys using in situ hybridization and a 253 bp human SERT cRNA probe. Monkeys (n = 5 animals/group) were ovariectomized and hysterectomized (spayed) and then untreated (control), or treated with E for 28 days (E treated), or treated with E for 28 days and supplemented with P for the last 14 days of the E regimen (E + P treated). Densitometric analysis of autoradiographs with gray-level thresholding was performed at five levels of the dorsal and median raphe. The number of pixels exceeding background in defined areas was obtained (pixel number). The average pixel number for spayed, E- and E + P-treated groups was 22,280 ± 3517, 15,227 ± 1714, and 14,827 ± 2042, respectively, in the combined dorsal and median raphe. In the E- and E + P-treated groups compared to the control group, there was a 32% and 33% decrease in SERT mRNA signal represented by pixel number (ANOVA, P < 0.05). Hence, E- and E + P-treated groups were significantly less than the control group, but they were not different from one another. Also, there were significantly fewer SERT mRNA-positive cells in the dorsal raphe of E- and E + P-treated groups (ANOVA, P < 0.001). Therefore E, with or without P, reduces SERT mRNA expression. These results suggest that the ability of P to increase prolactin secretion in E-primed monkeys does not involve an action at the level of SERT gene transcription. Hence, the mechanism by which the CNS transduces the action of P on prolactin secretion remains to be elucidated. However, these data suggest that one action of E replacement therapy in postmenopausal women may be to decrease expression of the SERT gene.