THE ROLE OF FETAL PARATHYROID HORMONE-RELATED PROTEIN IN TRANSPLACENTAL CALCIUM-TRANSPORT

During pregnancy, a placental calcium pump maintains the fetus in a hy percalcaemic 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 pro tein (PTHrP) has been implicated as the hormone responsible for mainta ining the placental calcium pump. In the present study on mice in whic h the PTHrP gene has been ablated by homologous recombination, we have measured both fetal and maternal circulating total and ionised calciu m levels, as well as fetal total body calcium, in order to determine w hether absence of PTHrP during fetal development has an effect on feta l calcium levels. Our results show that, in fetuses lacking PTHrP circ ulating ionised calcium levels are significantly lower than those of h eterozygote and wild-type littermates, but circulating total calcium l evels show no difference. Total body calcium levels of null mutants ar e significantly higher than those of normal littermates. The role of P THrP in maintaining the integrity of the transplacental calcium pump i n 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 s keletons of these animals. Alternatively, the increased avidity of the bones for calcium may in itself have produced a lower equilibrium lev el of available ionised calcium.