Defining the Roles of Parathyroid Hormone-Related Protein in Normal
Physiology.
Philbrick, W. M., J. J. Wysolmerski, S. Galbraith, E. Holt, J. J. Orloff, K.
H. Yang, R. C. Vasavada, E. C. Weir, A. E. Broadus, and A. F. Stewart.
Division of Endocrinology, Yale University School of Medicine, New Haven;
and Division of Endocrinology, The West Haven Veterans Affairs Medical Center,
West Haven, Connecticut.
APStracts 2:0008P, 1996.
ABSTRACT
Parathyroid hormone-related protein (PTHrP) was discovered as a result of a
search for the circulating factor secreted by cancers which causes the common
paraneoplastic syndrome humoral hypercalcemia of malignancy. Since the
identification of the peptide in 1982 and the cloning of the cDNA in 1987, it
has become clear that PTHrP is a prohormone that is posttranslationally
cleaved by prohormone convertases to yield a complex family of peptides, each
of which is believed to have its own receptor. It is also clear that the PTHrP
gene is expressed not only in cancers but also in the vast majority of normal
tissues during adult and/or fetal life. In contrast to the situation in
humoral hypercalcemia of malignancy in which PTHrP plays the role of a
classical "endocrine" hormone, under normal circumstances PTHrP plays
predominantly paracrine and/or autocrine roles. These apparent physiological
functions are also complex and appear to include [i]1[r]) regulation of smooth
muscle (vascular, intestinal, uterine, bladder) tone, [i]2[r]) regulation of
transepithelial (renal, placental, oviduct, mammary gland) calcium transport,
and [i]3[r]) regulation of tissue and organ development, differentiation, and
proliferation. In this review, the discovery of PTHrP, the structure of its
gene and its cDNAs, and the posttranslational processing of the initial
translation products are briefly reviewed. Attention is then focused on a
detailed organ system-oriented review of the normal physiological functions of
PTHrP.
APS Manuscript Number P-23-5.
Article publication scheduled January 1996 Physiological Reviews.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96