Aromatase in the human central nervous system

Sasano, Hironobu; Takahashi, Kazuhiro; Satoh, Fumitoshi; Nishimura, Hiroshi; Harada, N.

doi:10.1046/j.1365-2265.1998.00390.x

Cited by 123 publications

(86 citation statements)

References 33 publications

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“…Thus, small but consistent sex differences in SUV were detected in the brain, with higher values in all men relative to all women. Previous studies on postmortem brain samples (24,(30)(31)(32) reported similar levels of brain aromatase activity and gene expression in men and women. Conversely, results from animal studies demonstrated higher levels of brain aromatase in males and suggested that testosterone was a positive modulator of aromatase in the hypothalamic-preoptic area (6,7).…”

Section: Discussionmentioning

confidence: 81%

“…3.7 MBq/nmol at the time of injection). An arterial plasma input function for 11 C-vorozole was obtained from arterial blood samples withdrawn every 2.5 s for the first 2 min (Ole Dich automatic blood sampler) and then at 3,4,5,6,8,10,15,20,30,45,60, and up to 90 min (end of study). All samples were centrifuged to obtain plasma, which was counted, and selected samples were assayed for the presence of unchanged 11 C-vorozole.…”

Section: Pet Data Acquisition and Analysismentioning

confidence: 99%

“…Since other promoters besides the brain-specific exon 1.f (30) are expressed in the human brain, this heterogeneity may provide the basis for brain region-specific regulation of aromatase in humans, which may be exploited in the future to design organ-and region-specific interventions.…”

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confidence: 99%

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Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women

et al. 2015

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Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with 11 Cvorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aimed to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathologic situations can be studied. Methods: 11 C-vorozole (111-296 MBq/subject) was injected intravenously in 13 men and 20 women (age range, 23-67 y). PET data were acquired over a 90-min period. Each subject had 4 scans, 2 per day separated by 2-6 wk, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned after pretreatment with a clinical dose of the aromatase inhibitor letrozole. Time-activity curves were obtained, and standardized uptake values (SUV) were calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone, and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole-body radiation exposures were calculated using OLINDA software. Results: Liver uptake was higher than uptake in any other organ but was not blocked by pretreatment with letrozole. Mean SUVs were higher in men than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than SUVs in any other organ (ranging from 0.48 ± 0.05 in lungs to 1.5 ± 0.13 in kidneys). Mean ovarian SUVs (3.08 ± 0.7) were comparable to brain levels and higher than in any other organ. Furthermore, ovarian SUVs in young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, whereas aging and cigarette smoking reduced 11 C-vorozole uptake. Conclusion: PET with 11 C-vorozole is useful for assessing physiologic changes in estrogen synthesis capacity in the human body. Baseline levels in breasts, lungs, and bones are low, supporting further investigation of this tracer as a new tool for detection of aromatase-overexpressing primary tumors or metastases in these organs and optimization of treatment in cancer and other disorders in which aromatase inhibitors are useful.

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Section: Discussionmentioning

confidence: 81%

Section: Pet Data Acquisition and Analysismentioning

confidence: 99%

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Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women

et al. 2015

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“…In rodents, this reflects the fact that the sex-specific reproductive behaviors governed by these nuclei are activated by estradiol in males (where circulating testosterone up-regulates aromatase and, hence, its own metabolism to estradiol) as well as in females. Significant levels of aromatase are also found in other brain regions, including the amygdala, hippocampus, midbrain, and cortical regions in rodents, nonhuman primates, and humans, where its expression is steroid-independent and not significantly different in males and females Abdelgadir et al, 1997;Sasano et al, 1998;Stoffel-Wagner et al, 1999;Hojo et al, 2004;Yague et al, 2008;Roselli et al, 2009). Although this provides neuroanatomical evidence in support of a role for estrogens in regulating nonreproductive behaviors, it suggests that any sex differences are not likely to be dependent on differences in local aromatase activity.…”

Section: A Peripheral and Central Sites Of Synthesis Of Estrogens Inmentioning

confidence: 82%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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“…Adipose tissue has two alternative tissue-specific first exons; one is ∼70,000 bp upstream (exon I.4) [16], and the other is ∼250 bp upstream (exon I.3) [16,17] of the translation start site. The brain-specific first exon (1f) [18] lies ∼40,000 bp upstream [15], whereas in the gonads, the start site of transcription (in exon IIa) lies only 39 bp upstream of the start site of translation [19] (Fig. 1A).…”

Section: The Aromatase (Cyp19) Gene and Its Tissue-specific Expressionmentioning

confidence: 99%

Role of the progesterone receptor (PR) in the regulation of inflammatory response pathways and aromatase in the breast

Mendelson

Hardy

2006

The Journal of Steroid Biochemistry and Molecular Biology

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There is convincing evidence to suggest that estrogen and inflammatory mediators play important roles in growth and progression of breast cancer. Moreover, local conversion of androgens to estrogens by aromatase (product of CYP19 gene) occurs in 70% of all breast cancers. The actions of aromatase in both the breast tumor and in surrounding adipose stromal and endothelial cells can result in high local levels of estrogen production that stimulate tumor growth. The efficacy of current endocrine therapies is predicted only if the tumor contains significant amounts of ER. Presence of PR in the tumor also is an important predictor of tumor aggressiveness and responsiveness to endocrine therapy. Immunoreactivity for aromatase in human breast tumors is highly correlated with that for cyclooxygenase 2 (COX-2), the rate-determining enzyme in prostanoid biosynthesis. COX-2 expression also is correlated with expression of HER-2/neu, an oncogene expressed in >30% of breast tumors. In this manuscript, we will review findings suggest that induction of COX-2 by inflammatory cytokines acting through NF-κB contributes to the increase in CYP19 expression and breast cancer progression, and that PR plays a dominant protective role in breast cancer cells by antagonizing NF-κB activation of COX-2.

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Aromatase in the human central nervous system

Abstract: These results demonstrate that aromatase is expressed widely in various regions of human brain tissues in both men and women.

Cited by 123 publications

References 33 publications

Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women

Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

Role of the progesterone receptor (PR) in the regulation of inflammatory response pathways and aromatase in the breast

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Aromatase in the human central nervous system

Abstract: These results demonstrate that aromatase is expressed widely in various regions of human brain tissues in both men and women.

Cited by 123 publications

References 33 publications

Aromatase Imaging with [N-Methyl-11C]Vorozole PET in Healthy Men and Women

Aromatase Imaging with [N-Methyl-11C]Vorozole PET in Healthy Men and Women

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

Role of the progesterone receptor (PR) in the regulation of inflammatory response pathways and aromatase in the breast

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Product

Resources

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Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women

Aromatase Imaging with [N-Methyl-¹¹C]Vorozole PET in Healthy Men and Women