Effects of two synthetic parathyroid hormone-related protein fragments on maternofetal transfer of calcium and magnesium and release of cyclic AMP by the in-situ perfused rat placenta

Abstract

Two human parathyroid hormone-related protein (hPTHrP) fragments were tested for effects on maternofetal transfer of 45Ca and Mg across the in-situ perfused rat placenta at 21 days of gestation (term = 23 days). The fetal placental circulation was perfused with a Mg-free Krebs-Ringer solution and the unidirectional maternofetal clearance (Kmf) of 45Ca and Mg compared with that of 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with hPTHrP(1-34) (100 ng/ml) or hPTHrP(75-86)amide (50 ng/ml) did not significantly alter the Kmf of 45Ca or that of Mg. In separate rats, however, hPTHrP(1-34) but not hPTHrP(75-86)amide stimulated marked placental cyclic AMP (cAMP) release, the peak response of 63 +/- 7 pmol/min occurring 10 min after the beginning of the peptide perfusion. A lower dose of hPTHrP(1-34) (4 ng/ml) produced a similar peak release of cAMP, as did [Nle8,21, Tyr34]-rPTH(1-34)amide (4 ng/ml) and the adenylate cyclase agonist forskolin (17 mumol/l). Forskolin also rapidly increased the Kmf of 45Ca but not that of Mg or 51Cr-EDTA. The present study indicates that hPTHrP does not acutely affect maternofetal transfer of Ca or Mg across the perfused rat placenta. The data also question the role played by cAMP in the stimulatory actions of forskolin on placental Ca transport.

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…Mid-molecular PTHrP stimulated magnesium transport across in situ perfused ovine placentas (47,96,397) but not rodent placentas (611), and it did not affect placental phosphorus transfer (43,397,653). Placental transport of these minerals has not been examined in Pthrp null fetuses.…”

“…Exogenous PTH 1-34 did modestly stimulate calcium transport in perfused placentas from rat fetuses that had been decapitated to crudely mimic parathyroidectomy (554), but it had no effect in perfused placentas from intact fetuses (554,611). Placentas from thyroparathyroidectomized rat fetuses were not studied.…”

Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

“…In the fetal sheep, it has been shown to act on the placenta to regulate calcium transport (Rodda et al 1988). Although this does not appear to happen in the rat (Shaw et al 1991), absence of the PTHrP receptor in the mouse diminishes calcium acquisition by the fetus (Kovacs et al 1996). The similarity between our PTHrP data and the placental calbindin-D 9K mRNA towards term (significantly lower in DP rats, compared with increasing concentrations in CP rats) suggests that PTHrP might thus be a regulatory factor for placental calbindin-D 9K mRNA.…”

Parathyroid hormone-related peptide (PTHrP) regulates fetal–placental calcium transport through a receptor distinct from the PTH/PTHrP receptor

“…However, other investigators who studied intact fetal lambs (19,20) and artificially perfused placentas from decapitated (to mimic thyroparathyroidectomy) fetal rats (21,22) did not find an effect of the PTHrP mid-molecule on calcium transport. Instead, PTHrP-(1-86), PTHrP-(1-34), PTH-(1-34), and 1,25-D were found to have a small stimulatory effect on calcium transport.…”