The Emerging Role of Estrogens in Thyroid Redox Homeostasis and Carcinogenesis

Figure 2

Proposed model of estrogen-induced ROS generation increase in thyrocyte. Estradiol stimulates ROS production by NOX4 that is possibly located in the plasma membrane, endoplasmic reticulum, nuclear membrane, and mitochondria, as well as generates ROS through its own metabolization. ROS can reach the nucleus and promote several alterations that might contribute to thyroid carcinogenesis. Estrogen metabolization pathway also gives rise to the mutagenic DNA depurinating adducts. It is important to point out that the intracellular increase of ROS in response to estrogen can also positively modulate important carcinogenesis-related signaling pathways, such as ERK1/2 and PI3K/Akt. DSB: double-strand break; DUOX: dual oxidase; E2: estrogen; NOX4: NAPDH oxidase 4; ROS: reactive oxygen species; SSB: single-strand break; TPO: thyroperoxidase.