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Review
. 2021 Dec 23;2(1):189-202.
doi: 10.1089/andro.2021.0007. eCollection 2021.

Aromatase in the Human Brain

Iñigo Azcoitia  1 , Pablo Mendez  2 , Luis M Garcia-Segura  1   2
Affiliations
Review

Aromatase in the Human Brain

Iñigo Azcoitia et al. Androg Clin Res Ther. .

Abstract

The aromatase cytochrome P450 (P450arom) enzyme, or estrogen synthase, which is coded by the CYP19A1 gene, is widely expressed in a subpopulation of excitatory and inhibitory neurons, astrocytes, and other cell types in the human brain. Experimental studies in laboratory animals indicate a prominent role of brain aromatization of androgens to estrogens in regulating different brain functions. However, the consequences of aromatase expression in the human brain remain poorly understood. Here, we summarize the current knowledge about aromatase expression in the human brain, abundant in the thalamus, amygdala, hypothalamus, cortex, and hippocampus and discuss its role in the regulation of sensory integration, body homeostasis, social behavior, cognition, language, and integrative functions. Since brain aromatase is affected by neurodegenerative conditions and may participate in sex-specific manifestations of autism spectrum disorders, major depressive disorder, multiple sclerosis, stroke, and Alzheimer's disease, we discuss future avenues for research and potential clinical and therapeutic implications of the expression of aromatase in the human brain.

Keywords: aging; amygdala; cerebral cortex; hippocampus; hypothalamus; thalamus.

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Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.
FIG. 1.
Aromatase cytochrome P450 (P450arom) or estrogen synthase converts androgen c19 precursors in C18 estrogens. For instance, the enzyme converts androst-4-ene-3,17-dione (androstenedione) in estrone and testosterone into estradiol.
FIG. 2.
FIG. 2.
Representative examples of aromatase immunoreactive cells in the human brain. (A) Panoramic view of a section of the temporal cortex. Anti-aromatase immunoreactivity is observed in all cortical layers (1–6) and in the wm, but it is particularly intense in pyramidal cells of neocortical layers 2/3 and 5. In layer 1, aromatase immunoreactive cells, most of them with astrocyte morphology, are abundant in proximity of the pial surface (arrow). Female, 63 years old. (B) Cerebellar cortex. Intense immunoreactivity is observed in Purkinje neuronal perikarya in the PC and in their dendrites in the Mol, whereas granule cells are not immunoreactive. Immunoreactivity is also observed in interneurons in the molecular layer (arrowheads) and in a few neurons in the Gr (arrow), which may correspond to Golgi neurons. Male, 49 years old. (C) Pyramidal neurons in the Pyr of the hippocampal Ammon's horn CA1 region showing aromatase immunoreactivity in the perikaryon and in the basal and apical dendrites. Male, 65 years old. (D) Pyramidal neurons in the Pyr of the hippocampal Ammon's horn CA3 region showing aromatase immunoreactivity in the perikaryon and dendrites. Female, 43 years old. (E) Hippocampal dentate gyrus showing aromatase immunoreactivity in granule cell neurons in the Gr and a few interneurons in the Hil. Mol, molecular layer of the dentate gyrus. Female, 35 years old. All panels are from immunoperoxidase-stained sections using hydrogen peroxide as substrate and 3,3′-diaminobenzidine tetrahydrochloride as chromogen. In (B), the reaction was intensified by adding a small amount of nickel chloride. Gr, granular layer; Hil, hilus; Mol, molecular layer; Or, Stratum oriens; PC, Purkinje cell layer; Pyr, pyramidal layer; Rad, Stratum radiatum; Wm, white matter.
FIG. 3.
FIG. 3.
Aromatase immunoreactivity in astrocytes. (A) Panoramic view of the cortical white matter in the temporal lobe, showing immunoreactivity in cells with the morphology of fibrous astrocytes. (B) Detail of the layer 1 of the temporal cortex showing numerous immunoreactive astrocytes (arrowheads) in the proximity of the pial surface (arrows). (C) Immunofluorescence labeling of aromatase (green), the astrocyte cell marker GFAP (red), and the colocalization signal (yellow) in a cortical astrocyte. (D) Representative example of a fibrous astrocyte immunoreactive for aromatase in the cortical white matter. (E) Representative example of a protoplasmic astrocyte immunoreactive for aromatase in the cortical gray matter. All panels are from a 23-year-old male. GFAP, glial fibrillary acidic protein.
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