title: Estrogen and progesterone modulate monocyte cell cycle progression and apoptosis.
abstract: OBJECTIVE
  Pregnancy is characterized by dramatic immunologic changes most commonly characterized as suppression of cell-mediated immunity. Mechanisms of this immunosuppression are obscure but may be caused by increases in pregnancy-associated sex steroids such as 17-beta-estradiol or progesterone.
  
  
  METHODS
  Using five myelomonocytic cell lines in various stages of differentiation, the effects of 17-beta-estradiol and progesterone on cell cycling, apoptosis, and bcl-2 expression in randomly cycling cells before and after lipopolysaccharide (LPS) activation were examined.
  
  
  RESULTS
  Lipopolysaccharide alone inhibited cell cycle progression in THP-1 monocyte-like cells and U-937 histiocyte-like cells. Estrogen alone produced cell cycle arrest in all myelomonocytic cells except HL-60 pro-myelocyte-like cells. Progesterone had effects predominantly on pro-myelocytic-like HL-60 cells, inducing apoptosis. Estrogen and progesterone both decreased levels of bcl-2 in KG-1alpha, HL-60, and THP-1 cells. LPS partially antagonized both estrogen-induced THP-1 apoptosis and its suppression of bcl-2 protein.
  
  
  CONCLUSIONS
  Sex steroid-induced effects on cell cycle transition and apoptosis are potential mechanisms by which pregnancy-induced cell-mediated immune suppression may occur. Further investigation should provide a better understanding of pregnancy-induced immune changes and, perhaps, sex-based differences in monocyte function and immunologic responses.
authors.affiliation: Division of Rheumatology, G.V. (Sonny) Montgomery VAMC, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: T
authors.initials: T
authors.lastname: Thongngarm
authors.forename: J K
authors.initials: JK
authors.lastname: Jenkins
authors.forename: K
authors.initials: K
authors.lastname: Ndebele
authors.forename: R W
authors.initials: RW
authors.lastname: McMurray
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D020014:K562 Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011959:Receptors, Estradiol / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D011959:Receptors, Estradiol; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol