Abstract
In vitro studies show that estrogens acutely modulate synaptic function in both sexes. These acute effects may be mediated in vivo by estrogens synthesized within the brain, which could fluctuate more rapidly than circulating estrogens. For this to be the case, brain regions that respond acutely to estrogens should be capable of synthesizing them. To investigate this question, we used quantitative real-time PCR to measure expression of mRNA for the estrogen-synthesizing enzyme, aromatase, in different brain regions of male and female rats. Importantly, because brain aromatase exists in two forms, a long form with aromatase activity and a short form with unknown function, we targeted a sequence found exclusively in long-form aromatase. With this approach, we found highest expression of aromatase mRNA in the amygdala followed closely by the bed nucleus of the stria terminalis (BNST) and preoptic area (POA); we found moderate levels of aromatase mRNA in the dorsal hippocampus and cingulate cortex; and aromatase mRNA was detectable in brainstem and cerebellum, but levels were very low. In the amygdala, gonadal/hormonal status regulated aromatase expression in both sexes; in the BNST and POA, castration of males down-regulated aromatase, whereas there was no effect of estradiol in ovariectomized females. In the dorsal hippocampus and cingulate cortex, there were no differences in aromatase levels between males and females or effects of gonadal/hormonal status. These findings demonstrate that long-form aromatase is expressed in brain regions that respond acutely to estrogens, such as the dorsal hippocampus, and that gonadal/hormonal regulation of aromatase differs among different brain regions.
Highlights
Cytochrome P450 aromatase, the product of the CYP19 gene, catalyzes the biosynthesis of estrogens from androgens
Analysis of aromatase mRNA levels in ovaries from rats in different estrous cycle stages showed that aromatase expression was highest in proestrus, lowest in estrus, and intermediate in diestrus [F(2,3) = 9.82, p = 0.048, Figure 2A] with a statistically significant difference between proestrus and estrus (p,0.05). mRNA isolated from ovaries in diestrus was used in all subsequent quantitative realtime PCR (qPCR) experiments for comparison with brain regions
The present study investigated relative expression of mRNA for the long form of aromatase in distinct regions of the male and female rat brain and the effect of gonadal/hormonal status on aromatase expression in both sexes
Summary
Cytochrome P450 aromatase, the product of the CYP19 gene, catalyzes the biosynthesis of estrogens from androgens. Aromatase activity has been detected in the brains of both male and female rats, originally shown by Naftolin and colleagues [2]. Since this early work, numerous studies have investigated aromatase expression and/or activity in the central nervous system of multiple vertebrate species [3,4,5,6], including humans [7,8]. Aromatase has been reported in brain regions not closely linked to reproduction, such as the hippocampus and cerebral cortex [10,11,12]. This suggests that, in addition to reproductive functions, aromatase may play a role in modulation of mood, affective behaviors and/or learning and memory, which are supported by these non-reproductive brain areas
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