REGULATION OF SEROTONIN REUPTAKE TRANSPORTER MESSENGER-RNA EXPRESSIONBY 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 n eurons. 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 autor adiographs with gray-level thresholding was performed at five levels o f the dorsal and median raphe. The number of pixels exceeding backgrou nd in defined areas was obtained (pixel number). The average pixel num ber for spayed, E- and E + P-treated groups was 22280 +/- 3517, 15 227 +/- 1714, and 14 827 +/- 2042, respectively, in the combined dorsal a nd median raphe. In the E- and E + P-treated groups compared to the co ntrol group, there was a 32% and 33% decrease in SERT mRNA signal repr esented 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 S ERT mRNA-positive cells in the dorsal raphe of E- and E + P-treated gr oups (ANOVA, P < 0.001). Therefore E, with or without P, reduces SERT mRNA expression. These results suggest that the ability of P to increa se 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 replac ement therapy in postmenopausal women may be to decrease expression of the SERT gene. (C) 1998 Elsevier Science B.V.