Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by a 5α-reductase inhibitor

@article{Ishikawa2006AromataseindependentTC,
  title={Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by a 5$\alpha$-reductase inhibitor},
  author={Toshio Ishikawa and Christine A Glidewell-Kenney and J Larry Jameson},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  year={2006},
  volume={98},
  pages={133-138}
}
The androgen metabolite 5α-androstane-3β,17β-diol (3βAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance
TLDR
Results show that breast cancer cells deprived of estrogen up-regulate steroidogenic enzymes and metabolize androgens to estrogen-like steroids, a potential mechanism of resistance to aromatase inhibitors.
Increased androgen receptor and remodeling in the prostatic stroma after the inhibition of 5‐alpha reductase and aromatase in gerbil ventral prostate
TLDR
Results obtained following the long‐term inhibition of 5α‐r and Aro are relevant and highlight the actions of these enzymes as crucial not only for the maintenance of tissue architecture and ECM arrangement but also for androgen and AR function.
Enhanced formation of non-phenolic androgen metabolites with intrinsic oestrogen-like gene transactivation potency in human breast cancer cells: a distinctive metabolic pattern.
TLDR
The overall results demonstrated that MCF-7 cells exhibit enhanced expression and activity of androgen-metabolising enzymes, leading to rapid and large diol formation, and provide evidence that these androgen metabolites exert a potent oestrogens-agonistic effect, at genomic level, in oestrogen-dependent breast cancer cells.
Long‐term inhibition of 5‐alpha reductase and aromatase changes the cellular and extracellular compartments in gerbil ventral prostate at different postnatal ages
TLDR
The inhibition of 5α‐r and Aro enzymes affected, in a persistent manner, the structural and ultrastructural morphology of the prostate, irrespective of the gerbil′s age, and appear to be crucial in the maintenance of this gland during postnatal development.
Variable phenotypes associated with aromatase (CYP19) insufficiency in humans.
TLDR
Low residual aromatase activity may be sufficient for breast and uterine development to occur at puberty, despite significant androgenization in utero, according to functional studies revealed in the cases in which breast development occurred.
Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency.
TLDR
Current evidence does not support a role of naturally occurring estrogen elevations in testosterone deficiency or the treatment of elevated estrogens during testosterone therapy, and further research on the importance of estrogens in male sexual function is needed.
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References

SHOWING 1-10 OF 27 REFERENCES
Inhibitory effect of a novel non-steroidal aromatase inhibitor, YM511 on the proliferation of MCF-7 human breast cancer cell
Melatonin modulates aromatase activity in MCF‐7 human breast cancer cells
TLDR
It is concluded that melatonin, at physiological concentrations, decreases aromatase activity and expression in MCF‐7 cells, which makes this indoleamine an interesting tool to be considered in the prevention and treatment of hormone‐dependent mammary neoplasias.
Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor alpha.
TLDR
Transactivation assays with transfected ER-alpha reporter genes reveal a direct activation of ER- alpha by dehydroepiandrosterone (DHEA), 5alpha-androstene-3beta,17beta-diol, testosterone, and the two nonaromatizable androgens, dihydrotestosterone and 5 alpha- androstane-3 beta,17 beta-Diol.
Product of aromatase activity in intact LNCaP and MCF-7 human cancer cells
Effects of the aromatase inhibitor 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione in MCF-7 human mammary carcinoma cell culture.
TLDR
The steroid 7 alpha-APTA is an effective inhibitor of aromatase in intact MCF-7 cells and does not demonstrate any significant hormonal effects on the cells nor does this agent produce any general toxicological effects.
Human Osteoblast-Like Cells Express Predominantly Steroid 5α-Reductase Type 1
TLDR
This work investigated which isozymes were expressed in first passage hOB cells cultured from bone specimens obtained from six donors, and 5α-reductase isozyme expression in genital skin fibroblasts cultured from foreskin of three males was determined.
Steroid-Metabolizing Enzymes in Human Breast Cancer Cells. II. 5α-Reductase, 3α-Hydroxysteroid Oxidoreductase, and 17β-Hydroxysteroid Oxidor educt ase
TLDR
Characterization of these enzymes in MCF-7 cells indicated that the intracellular location, temperature and pH optima, cofactor requirements, and apparent substrate affinities for each are generally similar to those described in several other mammalian systems.
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