title: Macrophage secretions modulate the steroidogenesis of polycystic ovary in rats: effect of testosterone on macrophage pro-inflammatory cytokines.
abstract: OBJECTIVE
  The macrophage secretions' effect on ovarian steroidogenesis is investigated in a polycystic ovary syndrome rat model (PCO rat). The influence of testosterone environment on the expression of macrophage pro-inflammatory cytokines that participate in ovarian steroidogenesis is studied.
  
  
  METHODS
  PCO rats were induced by estradiol valerate. Spleen macrophages were cultured with and without testosterone (10(-6) M) and their secretions were used to stimulate ovaries from PCO and control rats. Ovarian hormones released and ovary mRNA levels of P450 aromatase and 3β-hydroxysteroid dehydrogenase were measured by radioimmunoassay and RT-PCR, respectively. The tumor necrosis factor alpha (TNFα) and nitric oxide (NO) levels in macrophage culture medium, along with the TNFα, interleukin (IL)-6, IL-10 and androgen receptors (AR) mRNA levels in macrophage cells were determined.
  
  
  RESULTS
  Macrophages from PCO rats released more TNFα and NO, expressed higher TNFα and IL-6, lower AR, and no change in IL-10 mRNA levels than control macrophages. TNFα, IL-6 and AR changes were greater after macrophage testosterone treatment. Macrophage secretions from PCO rats stimulated androstenedione and decreased estradiol release and ovarian mRNA P450 aromatase expression in PCO rats compared to macrophage secretions from control rats. These effects were greater when macrophages from PCO rats were treated with testosterone. Ovarian progesterone response was unchanged.
  
  
  CONCLUSIONS
  The differential steroidogenic ability of macrophage secretions from PCO rats is associated to the in vitro testosterone environment. Testosterone, probably acting on macrophage AR, induces a greater release of TNFα, modifying ovarian response by increasing androstenedione and slightly decreasing estradiol without affecting progesterone.
authors.affiliation: Laboratorio de Biología de la Reproducción y, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Figueroa
authors.forename: Roberto
authors.initials: R
authors.lastname: Davicino
authors.forename: Blas
authors.initials: B
authors.lastname: Micalizzi
authors.forename: Liliana
authors.initials: L
authors.lastname: Oliveros
authors.forename: Myriam
authors.initials: M
authors.lastname: Forneris
mesh_terms: D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007378:Interleukins / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007378:Interleukins; D009573:Nitrites; D011944:Receptors, Androgen; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D012313:RNA