The role of fetal parathyroid hormone-related protein in transplacental calcium transport.
During pregnancy, a placental calcium pump maintains the fetus in a hypercalcaemic state relative to the mother, a condition which has been thought to facilitate normal development of the fetal skeleton. Based on experiments performed in the sheep, parathyroid hormone-related protein (PTHrP) has been implicated as the hormone responsible for maintaining the placental calcium pump. In the present study on mice in which the PTHrP gene has been ablated by homologous recombination, we have measured both fetal and maternal circulating total and ionised calcium levels, as well as fetal total body calcium, in order to determine whether absence of PTHrP during fetal development has an effect on fetal calcium levels. Our results show that, in fetuses lacking PTHrP, circulating ionised calcium levels are significantly lower than those of heterozygote and wild-type littermates, but circulating total calcium levels show no difference. Total body calcium levels of null mutants are significantly higher than those of normal littermates. The role of PTHrP in maintaining the integrity of the transplacental calcium pump in the rodent thus remains unclear. It may be that the lower levels of fetal blood ionised calcium in mutant animals are due to disruption of the placental pump, but, if this is the case, compensatory mechanisms have operated to allow the excessive calcium deposition seen in the skeletons of these animals. Alternatively, the increased avidity of the bones for calcium may in itself have produced a lower equilibrium level of available ionised calcium.
Tucci
J
J
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Hammond
V
V
Senior
P V
PV
Gibson
A
A
Beck
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002678:Chimera; D005091:Exons; D005260:Female; D005838:Genotype; D006579:Heterozygote; D019868:Kanamycin Kinase; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D044162:Parathyroid Hormone-Related Protein; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000502:physiology*
D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase; D002118:Calcium