Parathyroid related hormone peptide (PTHrP) is a protein that is shares similar amino terminal structure to parathyroid hormone (1). PTHrP is located on chromosome 12p12.1-p11.2 and consists of 8 exons (2). PTHrP is expressed in many different fetal and adult tissues, including mammary glands, the heart, kidneys, pancreas, bones, and many more (3, 4). PTHrP is extensively involved in embryonic development of bone and teeth, and the stimulation of milk production in mothers (3, 5). PTHrP contributes to these developmental roles by increasing calcium reabsorption from maternal bones and teeth, and decreasing calcium excretion via the kidneys. This increase in calcium absorption can lead to malignant hypercalcemia in many cases (6). Hypercalcemia due to increased PTHrP expression via the placenta has also been shown during pregnancy. Blood calcium levels are quickly normalized following delivery (7). In mice, knockout of the PTHrP gene was associated with chondrodysplasia, reduced chondrocyte proliferation due to early maturation, and insufficient mammary growth in mothers (3, 5). High expression of PTHrP has been linked to certain cancers. Expression of PTHrP can lead to uncontrolled growth of intestinal cells, resulting in colon cancer in some patients (8). High concentrations of PTHrP have also been found in breast cancer metastases (9).
1. Juppner, H., A. Abou-Samra, M. Freeman, X. Kong, E. Schipani, J. Richards, L. Kolakowski, J. Hock, J. Potts, H. Kronenberg, and Al. Et. "A G Protein-linked Receptor for Parathyroid Hormone and Parathyroid Hormone-related Peptide." Science 254.5034 (1991): 1024-026. Web. 12 Apr. 2016. <http://science.sciencemag.org/content/254/5034/1024.full.pdf+html>.
2. "PTHLH Parathyroid Hormone-like Hormone [ Homo Sapiens (human) ]."NCBI. N.p., 3 Apr. 2016. Web. 14 Apr. 2016. <http://www.ncbi.nlm.nih.gov/gene/5744>.
3. Wysolmerski, J. J., Philbrick, W. M., Dunbar, M. E., Lanske, B., Kronenberg, H. and Broadus, A. E. (1998). Rescue of the parathyroid hormone-related protein knock out mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development. Development 125, 1285-1294.
4. Clemens, Thomas L., Sarah Cormier, Anne Eichinger, Karlhans Endlich, Nathalie Fiaschi-Taesch, Evelyne Fischer, Peter A. Friedman, Andrew C. Karaplis, Thierry Massfelder, Jérôme Rossert, Klaus-Dieter Schlüter, Caroline Silve, Andrew F. Stewart, Karen Takane, and Jean-Jacques Helwig. "Parathyroid Hormone-related Protein and Its Receptors: Nuclear Functions and Roles in the Renal and Cardiovascular Systems, the Placental Trophoblasts and the Pancreatic Islets." British Journal of Pharmacology 134.6 (2001): 1113-136. Web. 10 Apr. 2016. <http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0704378/epdf>.
5. Karaplis, A. C., A. Luz, J. Glowacki, R. T. Bronson, V. L. Tybulewicz, H. M. Kronenberg, and R. C. Mulligan. "Lethal Skeletal Dysplasia from Targeted Disruption of the Parathyroid Hormone-related Peptide Gene."Genes & Development 8.3 (1994): 277-89. Web. 10 Apr. 2016. <http://genesdev.cshlp.org/content/8/3/277.long>.
6. Martin, T. J. Properties of parathyroid hormone-related protein and its role in malignant hypercalcemia. Q. J. Med. New Ser., 76, 280: 771-786, 1990.
7. Eller-Vainicher, C., M. W. Ossola, P. Beck-Peccoz, and I. Chiodini. "PTHrP-associated Hypercalcemia of Pregnancy Resolved after Delivery: A Case Report." European Journal of Endocrinology 166.4 (2012): 753-56. Web. 14 Apr. 2016. <http://www.eje-online.org.ezproxy.library.tamu.edu/content/166/4/753.full.pdf+html>.
8. Calvo, Natalia, María Julia Martín, Ana Russo De Boland, and Claudia Gentili. "Involvement of ERK1/2, P38 MAPK, and PI3K/Akt Signaling Pathways in the Regulation of Cell Cycle Progression by PTHrP in Colon Adenocarcinoma Cells." Biochemistry and Cell Biology Biochem. Cell Biol. 92.4 (2014): 305-15. Web. 10 Apr. 2016. <http://www.ncbi.nlm.nih.gov/pubmed/25051885>.
9. Powell, Gerard J., Justine Southby, Janine A. Danks, Ross G. Stillwell, John A. Hayman, Michael A. Henderson, Richard C. Bennett, and John Martin. "Localization of Parathyroid Hormone-related Protein in Breast Cancer Metastases: Increased Incidence in Bone Compared with Other Sites." Localization of Parathyroid Hormone-related Protein in Breast Cancer Metastases: Increased Incidence in Bone Compared with Other Sites. N.p., 1 June 1991. Web. 12 Apr. 2016. <http://cancerres.aacrjournals.org/content/51/11/3059.long>.