Gonadotropin and its role in the ß-catenin/T-cell factor signaling pathway.

Gonadotropins, follicle-stimulating hormone and luteinizing hormone are key regulators in ovarian function, acting in an endocrine manner to regulate gametogenesis and steroidogenesis. In addition to normal tissue, gonadotropin receptors have also been demonstrated in ovarian carcinoma cell lines and primary tumors, suggesting that the gonadotropins may play a role in the pathophysiology of ovarian cancer. Thus, understanding mechanisms involved in signaling transduction by the gonadotropin receptors are of considerable interest and potential significance. In the ovary, gonadotropins initiate their cellular responses by binding to their G-protein-coupled receptors and activation of specific downstream intracellular effectors and signal pathways, including those of protein kinases A and C and mitogen-activated protein kinase. Recently, gonadotropins were shown to stimulate nuclear accumulation of ß-catenin, which controls lymphoid-enhancing factor/T-cell factor family-sensitive gene expression. ß-catenin has a pivotal function in the control of cell fate. The ability of gonadotropins to regulate ß-catenin provides a new dimension of knowledge linking pituitary hormones to the ß-catenin signaling in normal ovarian physiology and demonstrating how its dysregulation can contribute to the development of ovarian cancer.