Parathyroid Hormone-Related Protein: An Update

Abstract

PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes that are part of a larger "PTH gene family." This evolutionary relationship permits them to bind to the same type 1 PTH/PTHrP receptor, which explains why humoral hypercalcemia of malignancy resembles hyperparathyroidism. This review will outline basic facts about PTHrP biology and its normal physiological functions, with an emphasis on new findings of the past 5-10 yr. The medical and research communities first became aware of PTHrP because of its involvement in a common paraneoplastic syndrome. Now, research into the basic biology of PTHrP has suggested previously unrecognized connections to a variety of disease states such as osteoporosis, osteoarthritis, and breast cancer and has highlighted how PTHrP itself might be used in therapy for osteoporosis and diabetes. Therefore, the story of this remarkable protein is a paradigm for translational research, having gone from bedside to bench and now back to bedside.

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

“…Owing to the difficulties in the performance of the assays used to measure PTHrp in pregnancy, there has been debate on whether the circulating levels of PTHrp increase (20,21) or remain unchanged (22). The complications with the accurate measurement of PTHrp start by the expression of three different isoforms by the human gene (23). Each of these isoforms may be subjected to distinct post-translational processes and further breakdown and metabolic clearance.…”

Hormonal and Genetic Role Affecting the Bone Resorption in Patients with Osteoporosis

“…The receptors in the cell membrane bind to the stimuli from the outside and transmit the information to the cell nucleus through the transduction mechanism. Meanwhile, cell receptors (in the cytoplasm or nucleus) bind to hormone stimuli (usually steroid hormones) that pass through the cell membrane and into the cell to transfer the effector to the nucleus in which there is a steroid receptor complex bound to a specific deoxyribonucleic acid (DNA) of the gene sequence [12]. One of the factors that affect bone metabolism is the interaction of hormones anabolism (estrogen and testosterone) and hormones antianabolism (adrenal, glocorticoid and hydrocortisone).…”

“…Furthermore, the maintenance of dentures or dental prosthesis requires support of the jawbone. This support is not available in persons with osteoporosis [12].…”

The coexistence of hypercalcemia and hypoglycemia in a patient with a renal tumor and B cell lymphoma

“…Hypercalcemia associated with cancer can be classified into four types: 1) local osteolytic hypercalcemia, results from the marked increase of osteoclastic bone resorption in areas surrounding the malignant cells within the marrow space, 2) humoral hypercalcemia of malignancy (HHM) which is caused by systemic secretion of PTHrP, and causes increased bone resorption and enhances calcium renal retention 3) 1,25-dihydroxyvitamin D secretion by some lymphomas and 4) ectopic secretion of authentic PTH, a rare cause of hypercalcemia (6)(7)(8)(9). HHM is the most common cause associated with cancer (6-9,10).…”

“…PTHrP shares an homology of 60% in its terminal region with PTH and it can stimulate the same Type PTH/PTHrP receptor expressed in bone and kidney, mimicking the action of PTH by stimulating bone turnover through up-regulation of the expression of the receptor activator of nuclear factor-β k ligand (RANKL), and renal calcium reabsorption (9).…”