Ovarian steroid regulation of serotonin-1A autoreceptor messenger RNA expression in the dorsal raphe of rhesus macaques.

Abstract It is widely hypothesized that ovarian steroids act on serotonin neurons to modulate mood and alter neuroendocrine function in women. However, information is needed on the molecular consequences of estrogen and progesterone action in serotonin neurons. This study examined the effect of estrogen, with and without progesterone, on the expression of messenger RNA for the serotonin-1A autoreceptor in monkeys using in situ hybridization and a 432-bp serotonin-1A probe generated with polymerase chain reaction. Monkeys were spayed/ovariectomized (control; n =4), estrogen treated (28 days, n =4) and estrogen+progesterone treated (14 days estrogen+14 days estrogen+progesterone, n =4). Perfusion-fixed midbrain sections containing the dorsal raphe (10 μm) were hybridized at 60°C with 35 S antisense complementary RNA. After a final wash in 0.1 × standard saline citrate at 70°C, sections were apposed to βmax film for four days and then emulsion fixed. Adjacent sections were immunostained for serotonin to confirm the location of the dorsal raphe. Densitometric analysis of autoradiographs with gray level thresholding was performed at five levels of the dorsal raphe. The number of pixels exceeding background in defined areas was obtained (pixel number), as well as the mean optical density. In the estrogen- and the estrogen +progesterone-treated groups compared to the control group, there was a 38% and 43% decrease in serotonin-1A messenger RNA signal, respectively, represented by pixel number ( P P P P P These results suggest that estrogen reduces serotonin-1A gene expression and that the addition of progesterone further reduces serotonin1A gene expression in non-human primates. If the changes in gene expression are manifested by alterations in protein expression, then, together, these actions of estrogen and progesterone could increase serotonin neurotransmission, thereby elevating mood and/or altering neuroendocrine functions.