title: Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat.
abstract: OBJECTIVE
  The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied.
  
  
  METHODS
  Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro.
  
  
  RESULTS
  Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1β) and peritoneal (TNF-α, IL-1β, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-β by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-α and more IL-10, whereas peritoneal macrophages produced less IL-1β and TGF-β than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages.
  
  
  CONCLUSIONS
  Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro-inflammatory/anti-inflammatory cytokine secretory balance.
authors: Immunology Research Centre 'Branislav Janković', Institute of Virology, Vaccines and Sera 'Torlak', Belgrade, Serbia.
authors: Stanislava
authors: S
authors: Stanojević
authors: Immunology Research Centre 'Branislav Janković', Institute of Virology, Vaccines and Sera 'Torlak', Belgrade, Serbia.
authors: Vesna
authors: V
authors: Kovačević-Jovanović
authors: Immunology Research Centre 'Branislav Janković', Institute of Virology, Vaccines and Sera 'Torlak', Belgrade, Serbia.
authors: Mirjana
authors: M
authors: Dimitrijević
authors: Department of Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Vesna
authors: V
authors: Vujić
authors: Immunology Research Centre 'Branislav Janković', Institute of Virology, Vaccines and Sera 'Torlak', Belgrade, Serbia.
authors: Ivana
authors: I
authors: Ćuruvija
authors: Immunology Research Centre 'Branislav Janković', Institute of Virology, Vaccines and Sera 'Torlak', Belgrade, Serbia.
authors: Veljko
authors: V
authors: Blagojević
authors: Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors: Gordana
authors: G
authors: Leposavić
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D008264:Macrophages / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D016207:Cytokines; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; D001119:Arginase
keywords: Aged AO rats; cytokine production; iNOS/arginase activity; ovariectomy; peritoneal macrophages; splenic macrophages