On the role of brain aromatase in females: why are estrogens produced locally when they are available systemically?

Abstract

The ovaries are often thought of as the main and only source of estrogens involved in the regulation of female behavior. However, aromatase, the key enzyme for estrogen synthesis, although it is more abundant in males, is expressed and active in the brain of females where it is regulated by similar mechanisms as in males. Early work had shown that estrogens produced in the ventromedial hypothalamus are involved in the regulation of female sexual behavior in musk shrews. However, the question of the role of central aromatase in general had not received much attention until recently. Here, I will review the emerging concept that central aromatization plays a role in the regulation of physiological and behavioral endpoints in females. The data support the notion that in females, brain aromatase is not simply a non-functional evolutionary vestige, and provide support for the importance of locally produced estrogens for brain function in females. These observations should also have an impact for clinical research.

Low dose exposure to HBCD, CB-153 or TCDD induces histopathological and hormonal effects and changes in brain protein and gene expression in juvenile female BALB/c mice

“…In the brain, aromatase may play a pivotal role as it was shown that oestrogen is required for the maintenance, survival and the integrity of dopaminergic neurons [74,75]. Aromatization was also recently highlighted to be key for memory and learning in female organisms, which is mediated through both genomic and non-genomic actions of oestrogen [76]. Xenobiotics, which affect the conversion of oestrogen to testosterone and alter the T/E2 ratio, can therefore have a significant impact on brain health and disease [77].…”

“…An in vitro study pointed out that already at femtomole exposure to TCDD significantly decreased E2 secretion and mRNA expression levels of aromatase were detected in human luteinizing granulosa cells [79]. Interestingly, similar to PPAR-α, which regulates β-oxidation, aromatase activity is also regulated by Ca 2+ , which strongly inhibits aromatase at high but still physiological concentrations [76]. HBCD, CB-153 and TCDD have previously been reported to disrupt Ca 2+ homeostasis [12,18,80,81].…”

Cognitive Effects of Aromatase and Possible Role in Memory Disorders

“…This enzyme has now been discovered in several other brain regions. Under physiological conditions, aromatase is constitutively expressed in the neurons of reptiles, birds, and mammals ( 35 ). In mammals, CYP19 expression/aromatase activity has been detected in the hypothalamus, medial preoptic area, bed nucleus of stria terminalis (BST), MeA, prefrontal cortex, hippocampus, and cerebellum ( 35 , 39 – 46 ).…”

“…Under physiological conditions, aromatase is constitutively expressed in the neurons of reptiles, birds, and mammals ( 35 ). In mammals, CYP19 expression/aromatase activity has been detected in the hypothalamus, medial preoptic area, bed nucleus of stria terminalis (BST), MeA, prefrontal cortex, hippocampus, and cerebellum ( 35 , 39 – 46 ). Various brain regions of birds tend to express higher amounts of aromatase than in mammals, and thus avian models have greatly expanded our knowledge of how this enzyme regulates cognitive and other behavioral processes ( 35 ).…”

“…The focus of this review is the role of aromatase in regulating cognitive behaviors. Indeed, abundant literature implicates E2 in regulating various cognitive behaviors, especially in females ( 1 , 2 , 19 , 33 – 35 ). It is, however, beyond the scope of the current work to delve into the various mechanisms by which estrogens might affect learning and memory, including through membrane and/or nuclear estrogen receptors (GPER, ESR1, and ESR2).…”