TY - JOUR
T1 - Parathyroid hormone-related protein and its receptors
T2 - Nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets
AU - Clemens, Thomas L.
AU - Cormier, Sarah
AU - Eichinger, Anne
AU - Endlich, Karlhans
AU - Fiaschi-Taesch, Nathalie
AU - Fischer, Evelyne
AU - Friedman, Peter A.
AU - Karaplis, Andrew C.
AU - Massfelder, Thierry
AU - Rossert, Jérôme
AU - Schlüter, Klaus Dieter
AU - Silve, Caroline
AU - Stewart, Andrew F.
AU - Takane, Karen
AU - Helwig, Jean Jacques
PY - 2001
Y1 - 2001
N2 - The cloning of the so-called 'parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases.
AB - The cloning of the so-called 'parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify its therapeutic potential in a number of diseases.
KW - Beta cell
KW - Calcium-sensing receptor
KW - Cardiovascular system
KW - Cell proliferation
KW - Development
KW - Kidney
KW - Nuclear localization
KW - PTHrP
UR - http://www.scopus.com/inward/record.url?scp=0035181461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035181461&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0704378
DO - 10.1038/sj.bjp.0704378
M3 - Review article
C2 - 11704631
AN - SCOPUS:0035181461
SN - 0007-1188
VL - 134
SP - 1113
EP - 1136
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -