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Reproductive Sciences

, Volume 19, Issue 1, pp 86–91 | Cite as

Dehydroepiandrosterone (DHEA) Inhibition of Monocyte Binding by Vascular Endothelium Is Associated With Sialylation of Neural Cell Adhesion Molecule

  • Anna-Maria Curatola
  • Kui Huang
  • Frederick NaftolinEmail author
Original Articles

Abstract

Rationale: Adhesion of monocytes to vascular endothelium is necessary for atheroma formation. This adhesion requires binding of endothelial neural cell adhesion molecule (NCAM) to monocyte NCAM. NCAM:NCAM binding is blocked by sialylation of NCAM (polysialylated NCAM; PSA-NCAM). Since estradiol (E2) and dihydrotestosterone (DHT) induced PSA-NCAM and decreased monocyte adhesion, in consideration of possible clinical applications we tested whether their prohormone dehydroepiandrosterone (DHEA) has similar effects. Experimental: (1) DHEA was administered to cultured human coronary artery endothelial cells (HCAECs) from men and women. Monocyte binding was assessed using fluorescence-labeled monocytes. (2) HCEACs were incubated with E2, DHT, DHEA alone, or with trilostane, fulvestrant or flutamide. Expression of PSA-NCAM was assessed by immunohistochemistry and Western blotting. Results: Dehydroepiandrosterone inhibited monocyte adhesion to HCAECs by ≥50% (P < .01). Fulvestrant or flutamide blockade of DHEA’s inhibition of monocyte binding appeared to be gender dependent. The DHEA-induced expression of PSA-NCAM was completely blocked by trilostane. Conclusions: In these preliminary in vitro studies, DHEA increased PSA-NCAM expression and inhibited monocyte binding in an estrogen- and androgen receptor-dependent manner. Dehydroepiandrosteroneappears to act via its end metabolites, E2 and DHT. Dehydroepiandrosterone could furnish clinical prevention against atherogenesis and arteriosclerosis.

Keywords

atherosclerosis heart disease coronary estrogen androgen adhesion NCAM PSA-NCAM 

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Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Anna-Maria Curatola
    • 1
  • Kui Huang
    • 1
  • Frederick Naftolin
    • 1
    • 2
    Email author
  1. 1.Department of Obstetrics and GynecologyNew York UniversityNew YorkUSA
  2. 2.Department of Obstetrics and GynecologyNYU Langone Medical CenterNew YorkUSA

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