A. D. Care

The effects in the rat of two fragments of parathyroid hormone‐related protein on uterine contractions in situ

Synthetic parathyroid hormone fragment PTH(1–34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone‐related protein fragment PTHrP(1–34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine‐stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75–86 amide) (10(−9)−10(−7) M) was without effect, synthetic hPTHrP(1–34) (10(−9)−10(−7) M) was capable of inhibiting, in a dose‐related fashion, uterine muscle contractions precontracted with 10(−6) M‐acetylcholine. In a second series of experiments the bovine PTH(3–34) fragment itself was shown to have no stimulatory effect on acetylcholine‐stimulated contractions. Also this fragment in an equimolar concentration (10(−7) M) failed to antagonize the effects of PTHrP(1–34) on acetylcholine‐stimulated uterine contractions. However, a 100‐fold excess molar concentration of bPTH(3–34) (10(−6) M) completely abolished the inhibitory action of hPTHrP(1–34) (10(−8) M) on acetylcholine‐stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1–34) and PTHrP(1–34) on uterine contractions depends on the integrity of the amino‐terminal region of the molecule.

Fetal magnesium homeostasis in the sheep

The fetal plasma magnesium concentration exceeds that of the mother but the difference is small compared to that of ionized calcium concentration. Although not fully independent of changes in maternal magnesaemia, fetal magnesaemia showed a high degree of autonomy during both hypermagnesaemic and hypomagnesaemic changes induced in the ewe. As with calcium, the placental gradient is reversed after fetal thyroparathyroidectomy (TXPTX) with thyroxine replacement. During perfusion in situ of the placenta from such TXPTX fetuses isolated from the fetus itself, a stable positive placental gradient of magnesium concentration could be re‐established between the perfusing blood and the maternal circulation. As with calcium, this gradient could be increased by fetal calf parathyroid extract, parathyroid hormone‐related protein (PTHrP 1‐141), PTHrP (1‐84) but not by PTHrP (1‐34). It was concluded that a mid‐molecule portion of PTHrP can stimulate a putative placental pump which is responsible for the gradients of both calcium ions and magnesium across the ovine placenta.

The role of parathyroid hormone‐related protein in calcium homeostasis in the fetal pig

The concentrations of plasma parathyroid hormone‐like bioactivity and parathyroid hormone‐related protein (1–86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta.