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17-estradiol attenuates injury-induced microglia activation in the oculomotor nucleus

Additionally, ROS promotes tumor metastasis by interacting with VEGF under the influence of hypoxia-inducible factor-1 (HIF-1), inducing angiogenesis and facilitating tumor spread 64

doi: 10.1096/fj.11-184143

This means: The same dose stops working as effectively Higher doses may be required (not sustainable) Side effects or inflammatory signals may increase Cellular response plateaus or worsens Strategic cycling allows receptors to reset, restore sensitivity, and respond optimally to the peptide