CONICET | Buscador de Institutos y Recursos Humanos

Aims: The macrophage secretions´ effect on ovarian steroidogenesis is investigated in a polycystic ovary syn- 22 drome rat model (PCO rat). The influence of testosterone environment on the expression of macrophage pro- 23 inflammatory cytokines that participate in ovarian steroidogenesis is studied. 24 Main methods: PCO rats were induced by estradiol valerate. Spleen macrophages were cultured with and 25 without testosterone (10 26 −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 27 were measured by radioimmunoassay and RT-PCR, respectively. The tumor necrosis factor alpha (TNFα) and 28 nitric oxide (NO) levels in macrophage culture medium, along with the TNFα, interleukin (IL)-6, IL-10 and an- 29 drogen receptors (AR) mRNA levels in macrophage cells were determined. 30 Key findings: Macrophages from PCO rats released more TNFα and NO, expressed higher TNFα and IL-6, lower 31 AR, and no change in IL-10 mRNA levels than control macrophages. TNFα, IL-6 and AR changes were greater 32 after macrophage testosterone treatment. Macrophage secretions from PCO rats stimulated androstenedione 33 and decreased estradiol release and ovarian mRNA P450 aromatase expression in PCO rats compared to macro- 34 phage secretions from control rats. 35 These effects were greater when macrophages from PCO rats were treated with testosterone. Ovarian proges- 36 terone response was unchanged. 37 Significance: The differential steroidogenic ability of macrophage secretions from PCO rats is associated to the in 38 vitro testosterone environment. Testosterone, probably acting on macrophage AR, induces a greater release of 39 TNFα, modifying ovarian response by increasing androstenedione and slightly decreasing estradiol without 40 affecting progesterone