Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.

Parathyroid hormone-related protein (PTHrP) is initially translated as a preprohormone which is posttranslationally processed to yield a family of mature secretory forms. Most attention has focused on the aminoterminal portion of the molecule which is homologous to parathyroid hormone. It is clear, however, that a midregion species of PTHrP is posttranslationally cleaved from the highly conserved mid-region of PTHrP, and that the amino terminus of this peptide is Ala 38 . The purposes of the current study were three: 1) to confirm that Arg 37 immediately preceding Ala 38 serves as a posttranslational processing site in the PTHrP precursor, 2) to determine the carboxyl terminus of the mid-region secretory species of PTHrP, and 3) to synthesize this authentic mid-region secretory form of PTHrP and determine whether it is biologically active. The results indicate that: 1) Arg 37 is indeed a processing site in the PTHrP precursor; 2) three distinct mid-region PTHrP species are generated by posttranslational processing, PTHrP(38 -94)amide, PTHrP(38 -95), and most likely, PTHrP(38 -101); and 3) synthetic mid-region PTHrP(38 -94)amide is active in four different biological systems. These studies confirm the finding that PTHrP is a prohormone. More importantly, they define a novel, biologically active highly conserved mid-region secretory form of PTHrP.Parathyroid hormone-related protein (PTHrP) 1 was initially discovered through its structural and functional homology with parathyroid hormone (for a review, see Refs.

SUMMARYFactors affecting absorption of Mg from the ovine rumen have been studied using either a pouch constructed from part of the dorsal rumen or by an isolated washed rumen technique in vivo. Net absorption of Mg against the prevailing electrochemical gradient was observed. An increase in the K/Na ratio within the rumen led to an increase in the potential difference across the rumen wall, blood positive, and to a decrease in the net efflux of Mg from the rumen. This decrease was due to an increase in Mg influx into the rumen. The addition of ammonium chloride (30 mmol/l) to the rumen contents also led to a reduction in net Mg absorption but to no significant change in potential difference. The effects of high K/Na ratio and high ammonium ion concentration within the rumen were additive in causing decreases in net effluxes of both Mg and Na. An inverse relationship was demonstrated between the Ca concentration in the rumen and the net absorption rate of Mg. It was concluded that the efflux of Mg across the rumen wall depends at least in part on a functional system for Na transport.

SUMMARYPerfusion in situ of the placenta of intact or previously parathyroidectomized fetal lambs has been used to assess the ability of three mid-molecule fragments of the human parathyroid hormone-related protein (PTHrP)

SUMMARYPerfusion in situ of the placenta of previously thyroparathyroidectomized fetal lambs has been used to compare the ability of various forms of parathyroid hormone-related protein (PTHrP) to stimulate placental calcium transport. Whereas PTHrP (1-34) was without effect, PTHrP (1-141) was active but usually after a delay of up to 1 h, in common with the effect noted when using extracts of fetal parathyroid glands. In contrast, PTHrP (1-84) and PTHrP (1-108), tended to show a more rapid stimulatory action. It is suggested that post-translational processing of PTHrP (1-141) may occur as an activating step in the placenta in vivo.

SUMMARY The influence of plasma magnesium concentration on parathyroid gland function has been evaluated by perfusion at a constant rate of an isolated parathyroid gland in five goats and one sheep with whole blood of varying magnesium content. The concentration of magnesium in fresh whole blood was adjusted either by dialysis or by the addition of magnesium chloride before the perfusion. In each experiment, the concentration of calcium was maintained constant or was slightly altered to oppose the possible influence of magnesium on the rate of release of parathyroid hormone. Parathyroid hormone concentration in parathyroid venous plasma was estimated by a specific radioimmunoassay. In each experimental animal we observed that the concentration of parathyroid hormone in the effluent plasma diminished when the concentration of magnesium was raised or increased when the concentration of magnesium was lowered. These observations demonstrate a specific influence of magnesium on the rate of release of parathyroid hormone.

No abstract

No abstract