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 μmol/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. Journal of Endocrinology (1991) 129, 399–404