Reproductive Sciences

, Volume 19, Issue 4, pp 437–448 | Cite as

Increasing Evidence for and Regulation of a Human Placental Endogenous Digitalis-Like Factor

  • Jie Ma
  • M. Sean Esplin
  • C. David Adair
  • Lorrie A. Mason
  • Steven W. GravesEmail author


Endogenous digitalis-like factors (EDLFs) appear to be hypertensiogenic and increased in the serum and placenta of women with preeclampsia (PE), a complication of pregnancy. Digibind, an anti-digoxin antibody Fab fragment, reverses in vitro effects of EDLF and in vivo features of PE. We used Digibind in a radioimmunoassay to measure EDLF and compared this to a bio-functional assay of EDLF with good agreement. These methods confirmed that human placenta was a source of EDLF, synthesizing and releasing EDLF into the media of cultured human placental tissue. Ketoconazole, a steroid synthesis inhibitor, and 17-OH progesterone, a possible substrate of steroid synthesis, were shown to inhibit or increase EDLF release respectively, suggesting overlap of synthetic pathways. Abnormalities of PE such as placental hypoxia, increased reactive oxygen species and increased proinflammatory cytokines were demonstrated to increase placental EDLF release. These findings strongly support placental production of EDLF with increased release due to features of PE.


digitalis-like factors Digibind placenta ketoconazole 17-OH progesterone tumor necrosis factor-alpha reactive oxygen species hypoxia 


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Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Jie Ma
    • 1
  • M. Sean Esplin
    • 2
  • C. David Adair
    • 3
  • Lorrie A. Mason
    • 3
  • Steven W. Graves
    • 1
    • 4
    Email author
  1. 1.Department of Chemistry and BiochemistryBrigham Young UniversityProvoUSA
  2. 2.Department of Obstetrics and GynecologyUniversity of Utah School of MedicineSalt Lake CityUSA
  3. 3.Department Obstetrics and GynecologyUniversity of Tennessee College of Medicine, Baroness Erlanger HospitalChattanoogaUSA
  4. 4.ProvoUSA

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