Ezrin and the low-density lipoprotein receptor are regulated by estrogen and form a functional unit in pituitary GH3 somatolactotropes

Date of Completion

January 2006


Biology, Cell




In this thesis, the role of the cytoskeletal linker protein ezrin in the physiology of prolactin-secreting pituitary cells is investigated. First, the regulation of pituitary lactotrope morphology and function by estrogen is reviewed. Work identifying ezrin as a major estrogen-upregulated protein in pituitary cells is reported. An initial hypothesis, that ezrin acts to downregulate cell-cell adhesion molecules, is investigated and dismissed. The role played by ezrin-binding protein 50 (EBP-50), a protein that forms a complex with ezrin in other cell types, is investigated and found to be minimal in pituitary lactotropes. Finally, ezrin is shown to form a complex with another estrogen-regulated gene product, the low-density lipoprotein (LDL) receptor. The ezrin-LDL receptor complex is demonstrated to be critical for LDL endocytosis in cultured pituitary cells. A mechanism by which an ezrin-LDL receptor interaction might act to increase LDL uptake is postulated. Further experiments to more closely delineate the residues critical for ezrin-LDL receptor interaction and to establish a role for ezrin in the pathogenesis of hormone-sensitive cancers are proposed. ^