Estradiol synthesis within the human brain

doi:10.1016/j.neuroscience.2011.02.012

Neuroscience

Volume 191, 15 September 2011, Pages 139-147

https://doi.org/10.1016/j.neuroscience.2011.02.012 Get rights and content

Abstract

Estradiol biosynthesis is catalyzed by the enzyme aromatase, the product of the CYP19A1 gene. Aromatase is expressed in the brain, where it is involved not only in the control of neuroendocrine events and reproduction, but also in the regulation of neural development, synaptic plasticity and cell survival. In this review we summarize the existing data related with the detection of aromatase in human brain, with particular emphasis in the so-called “non-primary reproductive” areas. Besides hypothalamus, amygdala and preoptic/septal areas, aromatase is expressed in certain regions of basal forebrain, cerebral cortex, hippocampus, thalamus, cerebellum and brainstem of the human brain. Aromatase in human brain is produced by neurons, but there is also an astrocyte subpopulation that constitutively expresses the enzyme. The use of different methodological approaches, including the in vivo analysis by positron emission tomography of human subjects, has permitted to draw a general map of human brain aromatase, but the detailed distribution map is still far to be completed. On the other hand, despite the fact that there is only one aromatase protein, there are multiple mRNA transcripts that differ in the 5'-untranslated region, where regulatory elements reside. To date, some of the aromatase transcripts characteristic of cerebral cortex, as well as of human cell lines of neural origin, have been identified. This characteristic may confer tissue or even region-specific regulation of the expression and therefore it is conceivable to develop selective aromatase modulators to regulate the expression of the enzyme in the human brain.

This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Highlights

▶Human brain can synthetize estrogens by means of the enzyme aromatase. ▶Brain areas expressing aromatase express estrogen receptors also. ▶Locally synthetized estrogens are involved in synaptic plasticity. ▶Locally synthetized estrogens are involved in cell survival and neurogenesis.

Section snippets

Aromatase expression

Brain aromatase has been evidenced by enzyme activity assays, protein expression (immunocytochemistry, Western blotting), mRNA expression (in situ hybridization and reverse transcriptase-polymerase chain reaction) gene transcription and binding of radioactive labeled inhibitors that generate positron emission tomography (PET) images. There is not a complete correlation in the results obtained with these different techniques, which could be explained in terms of methodological limitations, but

Brain estrogen biosynthesis in the human brain: to what extent?

Comparing the heterogeneity in results obtained in different studies, the question is to determine how generalized is estrogen synthesis within the human brain. Is estrogen production only efficient when in large amounts, as in the hypothalamus, or even minute and extremely localized estrogen production matters, as it could be the case for synaptic plasticity modulation? Is the synthesis a sustained episode or rather a series of short events that could be misinterpreted as artifacts? Generally

Conclusion

Local estradiol synthesis in the human brain seems to be a more extended phenomenon than initially supposed. However, a detailed map of the human brain regions expressing aromatase is still missing. It is also unknown whether different promoters of the aromatase gene are used in different brain regions to regulate aromatase expression. The use of non-invasive in vivo techniques of determination paralleled with the systematic study of aromatase expression in postmortem brain or brain biopsies is

Acknowledgments

The authors thank Prof. Lydia DonCarlos for the critical reading of the manuscript. This work has been supported by grant BFU2008-02950-C03-01/02 of the Ministerio de Ciencia e Innovación, Spain.

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Brain Born EstrogensReviewEstradiol synthesis within the human brain

Abstract

Highlights

Section snippets

Aromatase expression

Brain estrogen biosynthesis in the human brain: to what extent?

Conclusion

Acknowledgments

Front Neuroendocrinol

Trends Neurosci

Prog Brain Res

Prog Neurobiol

Prog Neurobiol

Neuroscience

J Steroid Biochem

Mol Cell Neurosci

Neurobiol Aging

Neurobiol Aging

Nucl Med Biol

Steroids

Horm Behav

Biochim Biophys Acta

Biochem Biophys Res Commun

Front Neuroendocrinol

J Steroid Biochem Mol Biol

Prog Brain Res

Brain Res

J Steroid Biochem Mol Biol

Biochem Biophys Res Commun

Nucl Med Biol

Steroids

Trends Endocrinol Metab

Cell

Brain Res

Neurosci Lett

Neuroscience

Brain Res

Aromatase expression by reactive astroglia is neuroprotective

Ann N Y Acad Sci

Brain aromatase is neuroprotective

J Neurobiol

Blockade of estrogen receptor signaling inhibits growth and migration of medulloblastoma

Endocrinology

Roles of 17β-estradiol involve regulation of reelin expression and synaptogenesis in the dentate gyrus

Cereb Cortex

Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole

Synapse

Identification of aromatase in the reptilian brain

Endocrinology

Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system

Endocrinology

Novel promoter I8 and promoter usage in the CYP19 (aromatase) gene

Reprod Sci

Brain Born Estrogens
Review
Estradiol synthesis within the human brain