Title

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

Keywords

Biology, Cell

Degree

Ph.D.

Abstract

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. ^