Quantitative Analysis of Long-Form Aromatase mRNA in the Male and Female Rat Brain

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.

Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI

“…The amount of enzyme and its activity are heterogeneously distributed and the many variables controlling both of these aspects remain poorly understood (Charlier et al, 2013; Jacobson et al, 1997; Tabatadze et al, 2014). Nonetheless there is great appeal in using estrogen mimetics as therapeutics given its potency at promoting both cell proliferation and survival.…”

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

“…5-19.5 (E18.5-19.5) (Huhtaniemi, 1994;Scott et al, 2009); while in mice, the fetal testosterone peak occurs at E17-18 (O'Shaughnessy et al, 2006E17-18 (O'Shaughnessy et al, , 1998. Testosterone can be converted into estradiol in the CNS by the enzyme aromatase (Stanic et al, 2014;Tabatadze et al, 2014;Yague et al, 2010Yague et al, , 2008Yague et al, , 2004. Both steroids are able to regulate the differentiation of neurons and glial cells, generating sex differences in brain connectivity, structure and function (Dittrich et al, 2014;MacLusky and Naftolin, 1981;Sakakibara et al, 2013).…”

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

“…Nevertheless, different studies have shown large variability in aromatase levels in some brain regions (Shimotakahara et al 2004;Tabatadze et al 2014) and one study has provided indirect evidence of the efficacy of E2 synthesis in the adult cerebellum of rodents (Hedges et al 2012). In addition, no clear information is available as to the significance of low aromatase expression in regions of the adult brain like the PCs of the cerebellum (Sakamoto et al 2003).…”