Endocrinology and Metabolic Disorders

Thyroid carcinoma is 3-4 times more prevalent in women than in men and this preponderance can be linked to age, sex, iodine deficiency, and diet and radiation exposure. Certain factors like genetics, sex hormones and environment are reckoned to predispose a person to thyroid carcinoma. These data suggests the role of the sex steroid estrogen in the pathogenesis of thyroid carcinoma. It is clearly demonstrated that like breast and ovary, thyroid is also an estrogen responsive tissue. So in this study we checked the effect of 17-β Estradiol in the invasion of thyroid carcinoma. Cancer cell metastasis involves the formation of lamellipodia and filopodia. The formation of these structures is related to rapid activation of Ezrin/Radixin/Moesin (ERM) family of proteins. It is reported that ezrin was highly overexpressed in metastatic cancer cell lines when compared to poorly metastatic counterparts. We investigated influence of genomic and nongenomic actions of 17-β estradiol on ezrin. Genomic pathway is a long delayed process. Beyond the conventional genomic pathway, the nongenomic pathway of 17-β Estradiol is a transient process which lasts for few minutes. The phosphorylated ezrin can interacts and activates many signaling molecules which are important for cancer cell proliferation, invasion and metastasis. Further we have to investigate the upstream kinase causing the phosphorylation of ezrin and various expression patterns of ezrin and phosphoezrin ex vivo. Genomic pathway which is a long delayed process through ER alpha increased the expression of ezrin in a time dependent and dose dependent manner we observed a transient phosphorylation of ezrin by17-β Estradiol which lasts only for a few minutes. This process was sensitive to inhibitors. We observed that 17-β Estradiol can cause both the increased expression and activation of ezrin which occurs through the estrogen receptors suggesting that thyroid is also a target for estrogenic action. Such studies may lead to a new understanding of the pathogenesis of thyroid cancer and its female bias.