the 4.5 mg/ml of glucose control. 0.45 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19639295 and 0.0045 mg/ml of glucose both produced BTP phosphorescence that was lower than 0.045 mg/ml of glucose indicating that the relationship between glucose availability and intracellular oxygen concentration is parabolic. This parabolic relationship in terms of intracellular oxygen concentration and glucose availability may be due to the Crabtree effect. The cell is largely depend on glycolysis when glucose is plentiful but resorts to MedChemExpress Oleandrin oxidative phosphorylation when glucose starts to become limiting. This switch to oxidative phosphorylation under low glucose conditions is advantageous to the cell since the amount of ATP produced by oxidative phosphorylation is extremely high in comparison to the ATP yield from glycolysis. At high glucose concentrations it is more advantageous to produce energy by glycolysis rather than by oxidative phosphorylation so that the cell has adequate energy production without the production of harmful reactive oxygen species in the mitochondrial respiratory chain; this is considered to be caused by the Warburg effect. Androgen is One of the Regulators of Intracellular Oxygen Concentration Estrogens have been shown to be modulators of mitochondrial respiratory activity, and androgen receptor has been shown to influence metabolism in prostate cancer. However, the effects of androgen on the mitochondria remain largely undocumented. Both estrogen receptor and androgen receptor have been shown to localize to the mitochondria. Therefore, we hypothesized that androgen may be a modulator of mitochondrial function in LNCaP cells. As shown in Fig. 11A B, LNCaP in the presence of FCS showed a stronger ability to induce hypoxia surrounding the cells than the FCS-free control. In agreement with this finding, LNCaP in the presence of FCS showed stronger BTP phosphorescence than that in the absence of FCS, indicating stronger intracellular hypoxia in the presence of FCS. The association of estrogen, androgen, and estrogen receptor on mitochondrial function have been implicated, and LNCaP has been demonstrated to be androgen sensitive. However, whether estrogen and androgen can affect intracellular hypoxic status have yet to be demonstrated. Therefore, we hypothesized that androgen affects intracellular hypoxia in LNCaP cells. In microscopic studies using BTP, Mitochondria and Hypoxia 10 Mitochondria and Hypoxia R1881, a synthetic androgen, increased phosphorescence to approximately four times the control PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19639654 level indicating that R1881 induced hypoxia in the absence of FCS. Addition of flutamide, an inhibitor of the androgenandrogen receptor binding, in the presence of FCS reduced BTP phosphorescence indicating 
that flutamide reduced intracellular hypoxia to a level similar to the FCS-free control, possibly by blocking small amounts of androgen present in the serum or synthesized by LNCaP . The normal concentration of total testosterone in RPMI supplemented with 10% normal FCS has been reported to range from 55.1 to 97.5 pM; normal human males have a total testosterone level of 1035 nM. Flutamide in the absence of serum showed a slight increase in BTP phosphorescence relative to the serum-free control % versus 144549616316 %, respectively) implicating androgen synthesis from LNCaP. These data are the first to indicate that androgen is one of the modulators of cellular respiration and intracellular oxygen level. Here it should be pointed out that in vivo oxygen concentration within tissues rang
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