Elsevier

Placenta

Volume 18, Issue 7, September 1997, Pages 587-592
Placenta

Original article
Vascular effects of PTHrP (1–34) and PTH (1–34) in the human fetal-placental circulation

https://doi.org/10.1016/0143-4004(77)90014-5Get rights and content

Abstract

The aim of this study was to examine the vasodilatory effects of parathyroid hormone-related protein (PTHrP) (1–34) and parathyroid hormone (PTH) (1–34) on the human fetal-placental circulation utilising an in vitro placental perfusion model. In all experiments, the vasculature of an isolated human placental cotyledon was pre-constricted with the throm☐ane A2 mimetic U46619. A single dose of PTHrP (1–34) or PTH (1–34) (1.7–300 n m) was then infused into the fetal-placental circulation of the cotyledon. In other experiments, cotyledons were repeatedly infused with PTHrP (1–34) or PTH (1–34) (51.3 n m). Vasodilatory responses were significantly reduced in response to repeated exposure to PTHrP (1–34) and PTH (1–34) (P<0.001), indicating that this peptide desensitizes the fetal-placental vasculature. PTHrP (1–34) and PTH (1–34) equipotently stimulated a significant vasodilatation of the fetal-placental circulation (P<0.0001). The PTHrP receptor antagonist [Asn10, Leu11]PTHrP (7–34) (102 nM) was infused in U46619-constricted placentae in the presence and absence of PTHrP (1–34) (10.2 nM). The PTHrP antagonist alone had no significant effect in the fetal-placental circulation. The antagonist significantly attenuated the response to PTHrP (1–34) (P<0.015). Based on the data obtained in this study it is suggested that locally produced PTHrP (1–34) may be involved in the regulation of normal human fetal-placental vascular tone in an autocrine and/or paracrine fashion.

Reference (30)

  • BowdenS.J. et al.

    Parathyroid hormone-related protein in human term placenta and membranes

    Journal of Endocrinology

    (1994)
  • CaseyM.L. et al.

    Transforming growth factor-b1 stimulation of parathyroid hormone-related protein expression in human uterine cells in culture: mRNA levels and protein secretion

    Journal of Clinical Endocrinology and Metabolism

    (1992)
  • DunneF.P. et al.

    Parathyroid hormone related protein (PTHrP) gene expression in fetal and extra-embryonic tissues of early pregnancy

    Human Reproduction

    (1994)
  • FergusonJ.E. et al.

    Abundant expression of parathyroid hormone-related protein in human amnion and its association with labor

  • GermainA.M. et al.

    Parathyroid hormone-related protein mRNA in avascular human amnion

    Journal of Clinical Endocrinology and Metabolism

    (1992)
  • Cited by (28)

    • PTHrP is essential for normal morphogenetic and functional development of the murine placenta

      2017, Developmental Biology
      Citation Excerpt :

      Further, PTHrP is expressed very early on in embryogenesis and involved in multiple embryonic differentiation processes including blastocyst differentiation (Karperien et al., 1994; Philbrick et al., 1996; van de Stolpe et al., 1993). Additionally, PTHrP acts as a potent vasodilator of the fetoplacental vasculature to maintain low resistance blood flow (Macgill et al., 1997) and plays an important role in the regulation of fetal calcium homeostasis and placental calcium transport (Bond et al., 2008; Kovacs et al., 1996; Tucci et al., 1996). We, and others, have previously observed that Pthlh gene ablation in mice results in dysregulated fetal growth associated with marked skeletal and limb defects (Bond et al., 2008; Karaplis et al., 1994; Kovacs et al., 2001a; Lanske and Kronenberg, 1998).

    • Calcium-Regulating Hormones

      2011, Fetal and Neonatal Physiology E-Book, Fourth Edition
    • Vascular, Cardiovascular, and Neurological Actions of Parathyroid-Related Protein

      2008, Principles of Bone Biology: Volume 1-2, Third Edition
    View all citing articles on Scopus
    View full text