Clinical Reviews in Bone and Mineral Metabolism

, Volume 12, Issue 3, pp 142–164 | Cite as

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

Original Paper


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.


Pregnancy Lactation Fetus Neonate Placenta Mammary tissue 



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


Conflicts of interest

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

Animal/Human Studies

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


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Faculty of Medicine, Endocrinology, Health Sciences CentreMemorial University of NewfoundlandSt. John’sCanada

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