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The Role of PTHrP in Regulating Mineral Metabolism During Pregnancy, Lactation, and Fetal/Neonatal Development

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Abstract

Parathyroid hormone-related protein (PTHrP) was originally identified as the cause of humoral hypercalcemia of malignancy (HHM), a condition that resembles primary hyperparathyroidism and the effects of excess parathyroid hormone (PTH). But HHM is an unusual situation because PTHrP is normally undetectable in the circulation of the child or adult. Instead, most of PTHrP’s actions are now understood to be paracrine or autocrine, and not humoral. However, PTHrP is present in the circulation at measurable levels during fetal development, pregnancy, and lactation. During these time periods, PTHrP has humoral actions that regulate mineral and bone homeostasis independently of PTH. In fact, the existence of PTHrP was also predicted by the characteristic pattern of serum chemistries and PTH in cord blood of normal newborns, and by the normalization of calcium metabolism that temporarily occurs in hypoparathyroid women who breast-feed. This article reviews our present understanding about PTHrP’s role to control mineral and bone metabolism during pregnancy, lactation, and fetal development. Excess PTHrP can also be produced by the placenta or the breasts during pregnancy, or by the breasts during lactation, and in both situations it can lead to hypercalcemia and other clinical features that are indistinguishable from HHM. The highest concentrations of PTHrP are found in milk, and recent evidence indicates that milk-based PTHrP may reduce mineral accretion by the newborn skeleton, but whether it does this through local actions in the neonatal gut or after absorption into the neonatal circulation is unknown.

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Acknowledgments

Author has received grant support form Canadian Institutes of Health Research (No. 84253).

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Christopher S. Kovacs has no conflicts of interest or disclosures to make with respect to this work.

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This article does not include any studies with human or animal subjects performed by the author.

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  1. Faculty of Medicine, Endocrinology, Health Sciences Centre, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John’s, NL, A1B 3V6, Canada

    Christopher S. Kovacs

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Kovacs, C.S. The Role of PTHrP in Regulating Mineral Metabolism During Pregnancy, Lactation, and Fetal/Neonatal Development. Clinic Rev Bone Miner Metab 12, 142–164 (2014). https://doi.org/10.1007/s12018-014-9157-6

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