Urolithins: The Colon Microbiota Metabolites as Endocrine Modulators: Prospects and Perspectives.

Selective estrogen receptor modulators (SERMs) have been used in hormone related disorders, and their role in clinical medicine is evolving. Tamoxifen and raloxifen are the most commonly used synthetic SERMs, and their long-term use are known to create side effects. Hence, efforts have been directed to identify molecules which could retain the beneficial effects of estrogen, at the same time produce minimal side effects. Urolithins, the products of colon microbiota from ellagitannin rich foodstuff, have immense health benefits and have been demonstrated to bind to estrogen receptors. This class of compounds holds promise as therapeutic and nutritional supplement in cardiovascular disorders, osteoporosis, muscle health, neurological disorders, and cancers of breast, endometrium, and prostate, or, in essence, most of the hormone/endocrine-dependent diseases. One of our findings from the past decade of research on SERMs and estrogen modulators, showed that pomegranate, one of the indirect but major sources of urolithins, can act as SERM. The prospect of urolithins to act as agonist, antagonist, or SERM will depend on its structure; the estrogen receptor conformational change, availability and abundance of co-activators/co-repressors in the target tissues, and also the presence of other estrogen receptor ligands. Given that, urolithins need to be carefully studied for its SERM activity considering the pleotropic action of estrogen receptors and its numerous roles in physiological systems. In this review, we unveil the possibility of urolithins as a potent SERM, which we are currently investigating, in the hormone dependent tissues.

Role of phospho-ezrin in differentiating thyroid carcinoma.

Comprehensive theory explaining the relationship between estrogen (E2) and ezrin in metastasis of thyroid cancer remains non-elicited. In vitro results revealed that E2 could stimulate the expression and phosphorylation of ezrin in a time and dose dependent manner. Our data clearly showed that E2 enhanced the migration and invasion of cells, which was reversed by the transfection of cells with ezrin specific siRNA. Further, we observed that Phosphoinositide 3-kinase (PI3K) ROCK-2 are among the kinases responsible for E2 induced phosphorylation of ezrin. Clinical validation of ezrin/phospho-ezrin revealed that phospho-ezrin was intensely expressed in follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), while it was completely absent in follicular adenoma (FA) lesions in which the differentiation of the follicular neoplasms remains subtle. When histology of different carcinomas is correlated with benign FA with respect to phospho-ezrin, we observed that the marker was highly significant (p = 0.0001). 100% sensitivity, specificity and diagnostic accuracy of the above marker in the histological association of FTC, FVPTC with FA, enables us to suggest phospho-ezrin as a diagnostic marker to differentiate the follicular neoplasms. These data are the first to suggest the dynamic regulation of ezrin phosphorylation during metastasis in FTC.