Parathyroid Hormone related Protein (PTHrP) plays an important role in the body including intracellular regulation of calcium levels in brain cells, activating sensory and motor neurons and modulation of pain. Calcium is involved in the regulation of neurotransmitter release from the neurons, the process of aging, gene expression, muscle contraction and in signal transduction between cells in the body. Balance of calcium in cells and in the body depends on the action of the parathyroid hormone (PTH) and PTHrP.
In humans, PTHrP is produced in various tissues, including kidneys, bones, placenta, skin, brain and central nervous system. However, there is a controversy regarding the presence of the PTHrP in the CNS and its role in brain physiology and pathology.
Investigators at the ARUP Institute for Clinical and Experimental Pathology in Salt Lake City, Drs. Mark Kushnir, Lisa Peterson and Frederick Strathmann (F. Strathmann is currently employed at NMS Labs in Willow Grove, PA) conducted research with the aim of determining whether PTHrP is present in CSF, and if it correlates with PTHrP concentrations in serum. PTHrP and calcium were measured using mass spectrometry based methods in a collection of 140 paired human serum and CSF samples obtained from individuals without neurologic diseases. The results of the study are now published in the journal Clinical Biochemistry.
In this study, the authors determined that PTHrP is a normal constituent of human CSF with median CSF-PTHrP concentrations 51 fold higher than in serum; whereas, the observed median concentrations of Ca in CSF was 1.8 times lower than in serum. Concentrations of PTHrP in CSF and serum were positively correlated, suggesting that CSF could be a significant source of PTHrP in circulating blood. It was also observed that serum PTHrP concentrations were positively correlated with age and were significantly higher in women. In addition, the authors observed association between albumin indices and PTHrP-serum/PTHrP-CSF ratios.
Taken together, the results of the study indicate that PTHrP is a normal constituent of human CSF, that CSF PTHrP concentrations are much higher than in the serum and that CSF derived PTHrP may contribute to disorders of Ca regulation.
Dr Kushnir is Scientific Director, Mass Spectrometry R&D at ARUP Institute for Clinical and Experimental Pathology and Adjunct Assistant Professor at the Department of Pathology, University of Utah School of Medicine. Dr Mark Kushnir received PhD in Analytical Chemistry from Uppsala University (Uppsala, Sweden); his main areas of research include mass spectrometry and separation sciences; their application in clinical diagnostics, and evaluation of biomarkers of metabolic, endocrine and neurologic diseases. Dr Kushnir is author/coauthor of over 100 scientific peer reviewed publications.
Dr. Peterson is an Assistant Professor of pathology at the University of Utah School of Medicine and a medical director in the Immunology division at ARUP Laboratories. She received her PhD in experimental pathology from the University of Utah and completed a postdoctoral fellowship in the Department of Immunology at National Jewish Health and the University of Colorado School of Medicine in Denver. Dr. Peterson continued her training with a clinical immunology fellowship at the University of Utah. Her research interests include cellular immunology and autoimmune immunology, with a focus on autoimmune neurology.
Dr. Strathmann is currently the Vice President of Quality Assurance, Director of New Technology and Innovation, and Assistant Laboratory Director at NMS Labs in Willow Grove, Pennsylvania. As the Vice President of Quality Assurance at NMS Labs Dr. Strathmann oversees the Quality Assurance team members and helps plot the quality core mission of the company. As the Director of New Technology & Innovation, Dr. Strathmann manages the Innovation Team charged with growing and managing the innovation portfolio at NMS Labs. As an Assistant Laboratory Director, Dr. Strathmann is responsible for the overall clinical operation of the laboratory functional unit. Dr. Strathmann completed a ComACC accredited clinical chemistry fellowship at the University of Washington and is board certified in Clinical Chemistry and Toxicological Chemistry from the American Board of Clinical Chemistry.
Mark M. Kushnir, Lisa K. Peterson, Frederick G. Strathmann Parathyroid hormone related protein concentration in the human serum and CSF correlates with age Clinical Biochemistry 52 (2018) page 56–60