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Parathyroid hormone-related peptide increases urinary phosphate excretion in fetal lambs
M J Davicco1, V Coxam, J Lefaivre
1Mineral Metabolism Unit, INRA Theix, St-Genès-Champanelle, France.
Insights
Synthetic human parathyroid hormone-related peptide fragment (hPTHrP) and bovine parathyroid hormone fragment (bPTH) affect fetal lamb phosphorus levels. hPTHrP
Area of Science:
- Endocrinology
- Fetal Physiology
- Mineral Metabolism
Background:
- Parathyroid hormone (PTH) regulates calcium and phosphorus homeostasis.
- The role of parathyroid hormone-related peptide (PTHrP) in fetal development is not fully understood.
- PTHrP shares sequence homology with PTH and may interact with the PTH receptor.
Purpose of the Study:
- To compare the effects of synthetic human parathyroid hormone-related peptide fragment 1-34 (hPTHrP) and synthetic bovine parathyroid hormone fragment 1-34 (bPTH) on plasma and urinary inorganic phosphorus in fetal lambs.
- To investigate whether the effects of hPTHrP are mediated through the PTH receptor.
Main Methods:
- In utero chronic catheterization of fetal lambs (120-130 days gestation).
- Intravenous infusion of bPTH (6 nmol/fetus) or hPTHrP (6 nmol/fetus) alone or with [Tyr34]bPTH(7-34)NH2 (12 nmol/fetus).
- Measurement of plasma and urinary inorganic phosphorus, and assessment of diuresis and calcemia.
Main Results:
- Both bPTH and hPTHrP stimulated diuresis, induced hypercalcemia, hyperphosphaturia, and hypophosphatemia in fetal lambs.
- The effects of hPTHrP on phosphorus and calcium metabolism were inhibited by the synthetic PTH analogue [Tyr34]bPTH(7-34)NH2.
- These findings suggest a shared mechanism of action involving the PTH receptor.
Conclusions:
- hPTHrP exerts significant effects on mineral metabolism in the ovine fetus, similar to bPTH.
- The inhibitory effect of the PTH analogue suggests that PTHrP may act via the PTH receptor in the fetal lamb.
- This study provides in vivo evidence for the interaction of PTHrP with the PTH receptor during fetal development.
Abstract:
The effect of synthetic human parathyroid hormone-related peptide fragment 1-34 (hPTHrP) on plasma concentration and urinary excretion of inorganic phosphorus (P) was compared to that of synthetic bovine PTH fragment 1-34 (bPTH) in four 120- to 130-day-old fetal lambs chronically catheterized in utero. They received by I.V. infusion according to a Latin square design either bPTH (6 nmol per fetus) or hPTHrp (6 nmol per fetus) alone, or after the synthetic analogue [Tyr34]bPTH(7-34)NH2 (12 nmol per fetus). Control fetuses received the same volume of solvent alone. Both bPTH and hPTHrP stimulated diuresis. They induced hypercalcaemia, hyperphosphaturia and hypophosphataemia. The effects of hPTHrP were inhibited by [Tyr34]bPTH(7-34)NH2, indicating that PTHrP might work through the PTH receptor.