In vivo visualization of aromatase in animals and humans

Abstract

Aromatase catalyzes the last and obligatory step in the biosynthesis of estrogens across species. In vivo visualization of aromatase can be performed using positron emission tomography (PET) with radiolabeled aromatase inhibitors such as [11C]vorozole. PET studies in rats, monkeys and healthy human subjects demonstrate widespread but heterogeneous aromatase availability in brain and body, which appears to be regulated in a species, sex and region-specific manner. Thus, aromatase availability is high in brain amygdala and in ovaries of all species examined to date, with males demonstrating higher levels than females in all comparable organs. However, the highest concentrations of aromatase in the human brain are found in specific nuclei of the thalamus while the highest levels in rats and monkeys are found in the amygdala. Regional brain aromatase availability is increased by androgens and inhibited by nicotine. Future studies may improve diagnosis and treatment in brain disorders and cancers overexpressing aromatase.

Sex hormone levels are not associated with progression of renal disease in male patients with T2DM

“…Interestingly, E2 treatment has been shown to improve renal function in these animals [28]. However, interspecies differences in aromatase availability complicate any extrapolation of data derived from rodent experiments to human populations [29].…”

Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration

“…Therefore, it was revealed that the presence of fadrozole, or possibly another aromatase inhibitor, is crucial for the observed effect of testosterone on induced pluripotent stem cell-derived human neurons, indicating that these female neurons produce aromatase and are able to facilitate the conversion of testosterone to estradiol in vitro. The presence of aromatase activity here may be unsurprising, as the protective properties of aromatase have been described, though not in the process of MS, 32,44e46 and various studies have found ubiquitous aromatase expression within both the human brain 38 and cultured murine spinal motor neurons. 37 Furthermore, though estrogens are generally considered to confer neuroprotection, 22,23 our testosterone-only treatment groups both in vivo and in vitro displayed a disease course and cell death ratio nearly identical to that of control.…”

“…In our models, testosterone administered to female mice or applied to female-derived neurons is likely to be at least partly converted into estradiol due to endogenous or neuronal production of aromatase. 37,38 Our studies employ the aromatase inhibitor fadrozole to prevent this. Hence, in the context of the EAE and in vitro neuronal experiments, T þ FAD treatments provide a pure androgenic effect and T treatments one of mixed estradiol/ testosterone.…”

The effect of third-generation aromatase inhibitors on aromatase avtivity in visceral adipose tissue

“…Цей ферментний комплекс міститься в ендоплазматичному ретикулумі різних клітин, присутніх в яєчниках, плаценті, молочних залозах, матці, яєчках, мозку, жировій тканині тощо. Таким чином, у цих органах може відбуватися утворення естрогенів de novo або із транспортованих до них з інших тканин і депонованих там андрогенів (Biegon, 2016;Chan et al, 2016). Особливий інтерес у медицині викликає інтратуморальна ароматаза, зокрема, молочної залози.…”