Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15217, USA. taeschn@msx.dept-med.pitt.edu.
PTH-related protein (PTHrP) was originally discovered as the factor responsible for humoral hypercalcemia of malignancy. PTHrP is produced by most cell types and is a prohormone that gives rise to a family of mature secretory forms arising from posttranslational endoproteolytic cleavage of the initial translation product. Each of these secretory forms of PTHrP is believed to have one or more of its own receptors on the cell surface that mediates the normal paracrine, autocrine, and endocrine actions of PTHrP. Recently, evidence has accumulated that indicates that PTHrP is also able to enter the nucleus and/or the nucleolus and influence cellular events in an intracrine fashion. This review discusses the mechanisms by which PTHrP may gain access to the nucleus/nucleolus and the functional consequences of this nuclear entry by PTHrP.